In Enid, OK, taxidermist Max Alexander is working late in his shop as his German Sheppard, Colonel, looks on. Something moves in the shop and Max grabs his shotgun and goes to investigate. He doesn't find anything, but when Max returns to his workbench, a man wearing a cowboy hat steps out of the shadows. He easily knocks the shotgun out of Max's hands and sticks out a snakelike tongue. The intruder grabs Max, circling his chest with his arms, and crushes him to death.
At the Letters bunker, Dean brings Kevin after the Prophet gets drunk in Branson. Sam has been looking through news reports and finds a case for them, and Dean wonders if his brother is ready to hit the road again. Impatient, Sam says that he's fine and wants to head out hunting, and has found a report about Max's death. Dean isn't able to come up with a good reason to refuse without sounding suspicious and agrees.
When the brothers go to Max's shop in Enid, they find a protest sign painted on the doors in red paint. There's a symbol in the blood and Sam snaps a picture of it. They talk to the deputy, who lets Dean speak to Dave Stephens, the man who found Max's body. While Sam looks around, Dave explains that he comes by to pick up the entrails twice a week, and found Max's body. However, the entrail bins were empty, which is unusual on a hunting weekend. The deputy tells the Winchesters that nothing else was stolen except the entrails and the brothers suspect that a witch painted the symbol on the sign.
After Sam confirms that the sign belongs to an animal-right groups, SNART, the brothers go to see the co-founders, Dylan and Olivia Camrose. The Camroses own a vegan bakery and are both wearing sunglasses. The Winchesters tell them that their group sign was at the crime scene, and the couple insist that they didn't kill Max even though they didn't approve of what he did. The Camroses finally admit that they were at the taxidermy shop at the time of the murder. They heard someone hissing and when they went to investigate, the killer sprayed mace in their eyes. The couple remove their sunglasses and reveal that the skin around their eyes is badly scarred.
Back at their motel, Sam runs an Internet check on the type of injury and discovers that it is tissue necrosis, which is caused by venom rather than mace. They wonder if a snake is involved, but Sam points out that biting snakes and crushing snakes are two different species. Dean has his brother call Kevin to have him start doing research.
That night, the killer goes to the local animal shelter and pays off the clerk to take some cats. Among the dogs in the kennel are Colonel, Max's dog. The killer puts several cats into a burlap bag but then picks one up and considers it closely. Outside, the clerk hears the cat start yowling and goes to investigate. He arrives just in time to see the man swallow the cat whole. The killer spots the clerk and attacks him, ripping out his throat with clawed fingers.
The next day, Sam and Dean get a report on the newest murder and check out the shelter. The deputy informs them that all of the cats are missing. The Winchesters recognize Colonel and Dean tests it with a silver dollar to see if it's a skin walker, but the test proves negative. When the deputy comes over, Colonel starts barking at him. Dean quickly realizes that the dog is barking at the deputy's hat, and figures that the killer wore a similar hat. Sam gets an idea and calls Kevin, asking him to find a spell letting them talk to Colonel.
Back at their motel, the brothers get a call from Kevin, who has an Inuit spell that will allow them to read Colonel's thoughts. Sam wants to drink the resulting potion, but Dean insists on doing it. Once he performs the ritual, he tries to talk to Colonel and finally gets a response. The dog argues with him about glam metal bands until Sam interrupts. Colonel gives them a description of the killer at both murders, but can only describe the cowboy hat. However, the dog tells them that the killer smelled of red meat, tiger balm, and dishwashing detergent.
As Dean talks to Colonel, Sam wads up a paper napkin and tosses it in the trash. Dean picks it up and tosses it back to Sam, who does it instead. As they realize something strange is going on, a postman pulls up outside and Dean goes to the window to yell at him. Sam realizes what is happening and tells his brother that he's becoming a dog. They call Kevin and confirm that the spell has the side effect of giving the user some animal tendencies, and that no one knows how long the effects last.
As the brothers head back to the shelter to look for clues, Dean sees a pigeon pooping on the Impala and hears it mocking him. Colonel explains that all animals speak a universal language and that now Dean can understand them as well. Sam keeps Dean from shooting the pigeon and gets him into the car, and Dean hangs his head out the window as they drive to the shelter. When they arrive, both Dean and Colonel eye an attractive female poodle sitting across the street.
Inside, Dean interrogates the dogs, but most of them are unhappy to be locked up and don't have anything useful to say. One mutt calls them over and says that he can ID the killer, but demands a belly rub from Sam first. Once Sam starts in, the mutt tells them that the killer ate one cat and took the rest in a sack with the words "Avant-Garde Cuisine" on the side. Colonel has heard of the restaurant and tells the Winchesters that dogs aren't allowed there. As the brothers leave, Dean hesitates and then frees all of the dogs.
That night, the brothers break into the restaurant. A photo of the owner, Chef Leo, is on display and they realize that he is wearing a cowboy hat. Checking in the back, they find painkiller medicine hidden away. Dean finds some mice locked up in a cage, and they tell him to look in the refrigerator. All types of animal organs are marked and stored inside. Sam finds a book on shamanistic magic and discovers that it contains a ritual allowing the spellcaster to consume the organs of animals and gain their abilities. There are also cards labeled with various combinations of animals. When the Winchesters hear someone moving in the kitchen, they investigate and find a cook working. He explains that Leo is having a private dinner that night. A waiter comes in and the Winchesters claim that they're health inspectors on a surprise tour and tell both staff members to get out.
The brothers split up to search for Leo and flank him, but Leo blends into the wall using a chameleon's ability and then attacks him with his claws. The cook cuts Sam's throat, but Ezekiel takes over and heals the wound. Once the angel withdraws, Sam doesn't remember what has happened, but Leo wonders how he healed so quickly. He then punches Sam unconscious, figuring that he can absorb his healing ability.
As Leo ties Sam down and prepares to remove his organs, he smells dog and turns to see Dean. Thanks to his animal-enhanced reflexes, Leo subdues Dean and ties him to a support post with an extension cord. Dean sniffs at Leo and realizes that he has cancer, and the chef explains that his illness has gone beyond any conventional treatment. He went searching for a Pawnee shaman who taught him the spell, and Leo has been trying to find the right combination of animal abilities to cure himself. He admits that while he didn't set out to kill anyone, he's absorbed the instincts of various predators and will kill anyone who gets in his way.
As Dean tries to rub his bonds against the pillar, fraying them, he tells Leo that taking other people's lives won't make up for his own lousy life. Leo is convinced that he can heal himself if he consumes the unconscious Sam's organs, and takes out a wolf's heart. He eats it and casts the spell just as Dean frees himself and goes on the attack. Leo is too powerful for him and Dean runs off into the dining room. However, Dean whistles and every dog in the neighborhood comes running. They quickly corner Leo and tear him apart despite his abilities.
Dean goes back to Sam and wakes him up, and they take Colonel to the Camroses. The dog is less than thrilled to be adopted by hippies, but Dean assures him that he's getting a good home. Colonel thanks Dean for everything and starts to tell him the real reason that dogs are on Earth... and the spell wears off. Dean goes out to the Impala where Sam is waiting, and Sam wonders why Leo thought he was special. His brother passes it off as a crazy man's ramblings, noting that you can't reason with crazy, and tells Sam that he has nothing to worry about.