Dogs and cats are secretly highly intelligent, capable of speech, and maintain spy agencies to protect the world. In Germany, a bloodhound named Rex discovers a Cocker Spaniel puppy stealing secret codes. The thief reveals herself to be Kitty Galore, a hairless Sphynx cat, in disguise. After she escapes, Rex alerts the agents that he has spotted her. At a San Francisco used car dealership, the mascot Crazy Carlito (dressed like Uncle Sam) plans to bomb the building. Police officer Shane Larson and his dog Diggs arrive on the scene. Diggs recklessly retrieves the detonator from Carlito but bites it in the process, blowing up the building. Butch and Lou, now a fully grown Beagle and the head of D.O.G. HQ, watch the incident. Lou wants to recruit Diggs as an agent, and Butch reluctantly agrees.
Diggs is locked in the police kennels to prevent further accidents. Butch brings him to D.O.G. HQ. After tracking down a pigeon named Seamus with valuable information, Diggs and Butch meet a M.E.O.W.S. (Mousers Enforcing Our World's Safety) agent named Catherine, who is also in pursuit of Seamus. Catherine reveals that Kitty Galore is a former M.E.O.W.S. agent named Ivana Clawyu who fell into a vat of hair removal cream in a cosmetics factory when a guard dog chased her while on a mission. Humiliated by her fellow agents, Kitty left M.E.O.W.S. and, thrown out by her former family due to her appearance, vowed revenge on cats, dogs and humans.
Lou forms an alliance with Tab Lazenby, head of M.E.O.W.S, to take down Kitty Galore. At a cat lady's home, the team discover that Calico, Mr. Tinkles' former aid, has been sending stolen technology to Kitty via pigeons. Diggs attacks Calico, who tries to drown the team in cat litter. They escape and interrogate Calico, who claims not to know Kitty's whereabouts but does know where his former boss is.
The team travels to Alcatraz, where Mr. Tinkles, mentally ill from his time with Mr. Mason's maid and her sisters, is confined. While he refuses to directly help them, he provides one clue: "A cat's eye reveals everything." When Kitty Galore learns that the cats and dogs have joined forces, she hires mercenaries Angus and Duncan MacDougall to kill Seamus on the boat returning from Alcatraz. Diggs subdues Angus and accidentally throws him overboard. Fed up with Diggs' mishaps completely ruining the mission, Butch dismisses him from the team and leaves with Seamus to salvage clues.
Catherine takes Diggs to her home where he meets her nieces who tickle his tummy. He's surprised they do not hate him as a dog, Catherine says they have not learned to hate dogs yet. He reveals that past experiences have made him unable to trust anyone, leading to difficulty following orders and spending most of his life in kennels. Catherine assures him if he continues to think that way, no one will be able to help him. Diggs realizes his error, and follows Catherine to M.E.O.W.S. HQ, where they learn with help from the clue Mr. Tinkles gave them that Kitty is hiding at a fairground with her new owner, amateur magician Chuck the Magnificent.
At the fair, Diggs and Catherine are captured by Kitty and her assistant, Paws. Kitty reveals her plot to transmit the "Call of the Wild", a frequency only dogs can hear that will make them hostile to humans. Kitty believes humans will abandon these unwanted dogs in kennels. Kitty tries to use the fair's flying swings ride as a satellite dish to broadcast the signal to an orbiting satellite. Diggs and Catherine escape after Diggs confess his feelings to Catherine and are joined by Butch and Seamus. Seamus presses a red button, believing it will shut down the ride, but he instead activates Kitty's signal. Dogs around the world begin to react. Paws battles them, revealing he is a robot; Diggs tricks him into biting the device's wires, destroying the satellite. Kitty's pet mouse Scrumptious, fed up with Kitty's abuse, launches the cat, leaving her covered in cotton candy and landing in Chuck's hat. With the mission a success, Diggs goes to live with Shane. Upon returning to H.Q., Diggs learns Mr. Tinkles has escaped prison with Calico.
Joe Leydon of Variety called it "a faster, funnier follow-up" to the original film.[9] Scott Tobias of The A.V. Club negatively reviewed the film's plot, saying that "it's still about a feline plot for world domination, and the slobbering secret agents who stand in the way."[10] The film was nominated for a Golden Raspberry Award for "Worst Eye-Gouging Misuse of 3D", but it lost to The Last Airbender.
A third installment and stand-alone sequel, titled Cats & Dogs 3: Paws Unite!, features a new storyline taking place 10 years after the events of the previous film. However, unlike the previous two, the third film has been released as a straight-to-video release on digital on September 15, 2020, and on DVD and Blu-ray on October 13. It is also the only film that does not have any of the original cast members from the previous films. The new voice cast includes Melissa Rauch, Max Greenfield and George Lopez. It was directed by Sean McNamara, co-produced by Andrew Lazar and David Fliegel, and written by Scott Bindley. It was distributed by Warner Bros. Home Entertainment. The film received a nationwide theatrical release in Australia on September 24, and in the United Kingdom on October 2.
Kitty Galore, formerly an agent for cat spy organization MEOWS, has gone rogue and hatched a diabolical plan to not only bring her canine enemies to heel, but take down her former kitty comrades and make the world her scratching post.
At a satellite base in Northern Germany, a worker named Freidrich (Fred Armisen), delivering secret codes finds a labrador puppy outside his office. He brings the puppy inside, showing her to his pet bloodhound Rex (voiced by Len Morganti). Rex senses something is wrong with the puppy and starts to bark at her, making the worker take him outside. Both are locked out of the office. Rex looks in the window, seeing the puppy taking pictures of the top secret documents and later revealing to be Kitty Galore (voiced by Bette Midler), a female hairless cat. Rex is revealed to be a dog agent and reports to HQ.
In San Francisco, Diggs (voiced by James Marsden), a German Shepherd police dog and his owner Shane Larson (Chris O'Donnell) are called to a hostage situation at Crazy Carlito's used car lot. Diggs deliberately ignores Shane's commands, attacking Crazy Carlito (Paul Rodriguez) and making him release a device that Diggs grabs, which makes the car lot office blow up. Butch (voiced by Nick Nolte) and Lou (voiced by Neil Patrick Harris) are watching footage of the incident. Lou, no longer a field agent having been promoted to official level hence being termed "desk jockey" by Butch, wants Diggs to be an agent with Butch as his mentor (to his reluctance) to help defeat Kitty Galore.
At the police station, Diggs is suspended and sent back into the kennels. Shane wants to adopt Diggs, but the police will not allow it. Butch recruits Diggs and takes him to HQ. Lou gives them a mission to track down a stool pigeon named Seamus (voiced by Katt Williams), who is an informant for the dogs and apparently is being hunted down by Kitty Galore.
After tracking down Seamus, Diggs and Butch meet a M.E.O.W.S. agent named Catherine (voiced by Christina Applegate), who was after Seamus for the same reason the dogs were. She reveals that Kitty was once an agent named Ivana Clawyu who worked for M.E.O.W.S. until about a year ago; Ivana was on a mission at a cosmetics factory during which a guard dog chased her into a vat of hair removal cream causing her to lose all her fur and give her the appearance of a Sphynx cat. Unrecognizable and humiliated by her cat comrades, she left M.E.O.W.S. to return to her human home at Christmas, but unfortunately was kicked out. Since then, Kitty went rogue and has been plotting her revenge on not only dogs, but cats and humans as well.
Needing help to find out where Kitty could be hiding, they go see Mr. Tinkles (voiced by Sean Hayes) who is locked up, in a similar fashion as Hannibal Lecter in Silence of the Lambs, at a hidden prison on Alcatraz Island (he was presumably sent there from developing insanity from his torturous time with Mr. Mason's maid and her sisters since the first film). Though he refuses to tell them Kitty's exact location, he gives a hint to the group that "a cat's eye reveals everything" and that he is planning his escape. Kitty discovers through an informant at the prison that the cats and dogs are working together and sends two Scottish orange tabby cat mercenaries named Angus and Duncan MacDougall (voiced by Michael Beattie and Jeff Bennett) to attack them and capture (and possibly assassinate) Seamus on the boat returning from the prison. After getting fed up with Diggs not listening to his commands (letting a carrier pigeon lead get away, almost getting the team drowned in a kitty litter death trap and letting the MacDougall Twins escape), Butch angrily dismisses him and leaves with Seamus to the pigeon's home to find clues, leaving Catherine with Diggs. Catherine takes Diggs to her home. Diggs is proven ticklish when Catherine's nieces tickle his tummy. Catherine discovers that Diggs has been in and out of kennels his whole life due to the fact that he never trusted anyone but himself. She then takes him to the Cat HQ. Diggs, Catherine and Tab learn that Kitty is hiding at a fairground with her new master, a magician named Chuck the Magnificent (Jack McBrayer), from a still picture from her video - by looking in the eyes like Mr. Tinkles said.
Not long after arriving at the fairground, Diggs and Catherine are captured by Kitty and Paws. Meanwhile, Butch discovers blueprints for a giant satellite dish in Seamus' home (this was the reason Kitty was after Seamus, his cousin stashed the blueprints there). Back at the fairground, Kitty reveals to Diggs and Catherine that she plans to send a signal (which she named "The Call of the Wild") that only dogs can hear through televisions, radios, and cell phones via an orbiting satellite, to make them act hostile towards their humans so that all the dogs will be put in the kennels. After escaping Kitty's death trap, Diggs and Catherine meet up with Butch and Seamus, who were alerted by Lou and Tab.
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