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In Beverly Hills, California, wealthy businesswoman Vivian "Viv" Ashe leaves her richly pampered pet chihuahua, Chloe, with her irresponsible niece, Rachel, while she embarks on a business trip for ten days. Papi, the landscaper Sam's pet Chihuahua, has an unrequited crush on Chloe, by which she is disgusted. On a whim, Rachel decides to go to Mexico with her friends and brings Chloe along. When Rachel leaves Chloe alone in the hotel room to go dancing at a club, Chloe goes looking for her, but gets dognapped as she tries to find Rachel and is sent to the dog fights in Mexico City. There, she meets a street-smart German Shepherd named Delgado. Rachel comes back to the hotel and is frantic when she finds Chloe missing.

Chloe is picked to fight in the pit against El Diablo, a fierce Argentinean-Bolivian Doberman Pinscher. Delgado helps her escape the dog fights, unleashing the other dogs from their cages and unlocking the ring to allow both Chloe and himself to flee. After several arguments, he then decides to return her to Beverly Hills safely. Meanwhile, Rachel and Sam go to the Mexican police and offer rewards in an effort to find Chloe. El Diablo is sent by the dog fight ringleader, Vasquez, to capture Chloe and obtain the reward.

Chloe and Delgado split up when Delgado goes to get help to return Chloe to Beverly Hills. While he is gone, Chloe saves a pack rat named Manuel from being eaten by an iguana named Chico. Manuel gratefully offers to take Chloe's collar to a ship for the captain to read it, and Chloe accepts. When Delgado returns and finds out what happened, he explains that it was all a con to steal Chloe's expensive collar, and that in reality, iguanas are vegetarians.