Charlie and Tommy
Tommy Spinelli is a made man, wiseguy hired by a pair of dimwitted hitmen to transport a duffel bag full of decapitated heads across the country to a crime boss (as proof of the deaths). As Spinelli gets on the plane, he meets Charlie Pace, a friendly, talkative, young English touring musician who is going to Mexico to see his girlfriend Laurie and her parents the Bennetts. Unfortunately for Spinelli, the bag gets switched with an identical bag belonging to Charlie. Spinelli calls Charlie's frat house and speaks to his friend Ernie who gives him little help and irritates him over the phone. Spinelli travels to London, England to get information out of Charlie's friend Ernie.
Spinelli calls the hitmen requesting more time; he is told he has one day to recover the heads or he is dead. Meanwhile, Charlie is with his girlfriend's parents at a Mexican beach motel where his girlfriend informs him that she planned to dump him and he only came out of a misunderstanding he had. Charlie tells his girlfriend she feels that way only because her parents dislike him and to just wait till they left to finalize her decision.
Mrs. Bennett, while hiding a birthday gift for her husband discovers Charlie's bag with the heads inside and believes Charlie to be a murderer, prompting her to attack Charlie in an attempt to protect herself and her family. Meanwhile, Spinelli arrives at Charlie's frat house to meet with Ernie and another of Charlie's friends Steve and interrogates them. At the hotel, Mrs. Bennett is sedated and given bed rest, Mr. Bennett thinking her outburst was due to her alcoholism. Mr. Bennett makes a call to his mother inviting her to the hotel and Charlie discovers the heads inside the bag and with Laurie plans how to dispose of them.
After a round of torture, Spinelli has Steve and Ernie call up everyone Charlie knows in the hopes to find him. Mr. Bennett goes to check in on his wife who tells him that Charlie is a mass murderer with body parts in his bag. Mr. Bennett takes his wife and they inspect Charlie's room and when they come up with nothing, Mr. Bennett convinces his wife it was a trick of her mind due to the medication she was taking.
After an unsuccessful attempt to bury the heads in the desert, Charlie calls his friends for advice. Spinelli picks up the phone and tells Charlie he wants his heads back. They set up a meeting at the airport and Charlie admits to Spinelli he lost one of the heads. Needing a new head to replace the one Charlie lost, but not knowing where any are, Ernie suggest breaking into the cryonics lab to find heads, not knowing that Charlie had recovered the missing head already.
At the airport, Mr. Bennett takes a bag with several heads and puts it through the x-ray machine where security sees it and arrests Mr. Bennett. At the cryonics lab and the morgue Spinelli has Ernie and Steve take heads from corpses to replace the head Charlie may have lost, taking many heads not knowing whose head Charlie lost. Back at the hotel, Charlie, Laurie, Mrs. Bennett, and Mr. Bennett's mother speak to Mr. Bennett's lawyer who tells them that Mr. Bennett confessed to murder after being tortured, and was sentenced to death. Ernie, Steve, and Spinelli return to the frat house with their heads and formulate a plan to have Steve fly them to San Diego airport using his pilot's license.
On the phone, the two hitmen talk to Big Sep and he tells them that he wants to see the heads. On the news the two hitmen see Mr. Bennett on the news arrested with two of the eight heads and begin to worry what Big Sep will do. Charlie calls Spinelli, who arrived at the airport and confessed he lost two heads, but had retrieved the one he lost earlier. Spinelli tells him not to move and not to lose any more heads or he would replace them with his family and friends. Charlie promises Laurie that he will prove her father's innocence. Mrs. Bennett charges into the room and tells Charlie she is calling the police; Laurie hits her with a vase and knocks her out. Charlie goes to rent a car, finding the car that was stolen from him earlier.
Spinelli comes to the hotel with a demand to see Charlie who is on his way to the border to hand off the heads to the police. The two hitmen who came to San Diego to find Spinelli rent a car and spot him at the hotel. Spinelli drives with Ernie, Steve, and the Bennett family to meet Charlie at the drop off point. Charlie is stopped in the road and carjacked by the same criminals as before, but they leave the car when they noticed the heads in the cooler.
Spinelli spots Charlie by the side of the roads and demands the heads. Charlie admits to loosing yet another head to a coyote who took one from the cooler. While searching for the coyote Spinelli spots the two hitmen, realizing he is in deep trouble. Charlie suggests they team up and Spinelli reluctantly agrees. Spinelli takes the heads and goes to a motel with the hitmen outside watching him.
The next morning Spinelli stops at the hotel and has breakfast while waiting for the two hitmen. When they show up Spinelli tells them he will not give them the heads and that he will complete the delivery. Charlie comes into the hotel and with Spinelli's gun takes the heads back and drives towards the border to turn them into the police.
At the airport Charlie runs up to the officers and gives them the bag. The hitmen show up and claim the bag as theirs and the police arrest them. The police open the bag to find one of the heads Spinelli took at the cryonics lab. Charlie and Spinelli give each other a thumbs up on a plan gone right,and Spinelli walks to his plane with the heads in his bag.
In the credits, Charlie and Laurie are seen on their wedding day. Mr. Bennett present with a shaved head from his time in the Mexican prison. Mr. Bennett's mother, still alive from when Spinelli threw her from a truck, sitting at a guest table. Steve, in a straight jacket, believed to be insane from the experience. Mrs. Bennett clean, happy, and sober. Ernie is seen walking out of an operating room, now as a doctor. And Spinelli on a beach enjoying his retirement.