Hector's helping to load stuff into a truck, getting ready to go white river rafting with his cousin and two friends: Hector and Jimmy. Hector feels a weird pain.
Two workers from the Appendix Lodge, under the supervision of the big boss Billy Blob, are hammering a phony detour sign into Hector to drum up business for the Appendix Lodge.
Drix's preparing to go camping, catching Ozzy unaware. Ozzy doesn't want to go. Drix gets upset and Ozzy says he'll go. Maria will be joining them.
Drix, Maria and Ozzy are hiking in the wilderness. Drix is over-reacting to everything. Drix tells Ozzy after he trips that the first rule is to watch your step and Ozzy says that the second rule is to never leave the city. They head to Bladder Falls.
Maria, Ozzy and Drix are canoeing and Drix is over-reacting again, but having fun. Ozzy says there's only 47 hours and 52 minutes of "fun" to go.
Hector and company are white river rafting when Hector moans. Travis tells Hector he shouldn't have eaten beef jerky for breakfast, but Hector says it's only a cramp.
The Appendix Lodge is booming with business. Uncle Billy Blob, the owner, is sweet-talking guests into staying.
Maria, Ozzy and Drix are canoeing. Maria and Ozzy think they're lost and Ozzy and Drix start fighting and fail to notice Maria warning them of the upcoming rock. They flip out and lose the canoe. They all start arguing and no one talks to each other.
Hector and company are eating around the campfire. Hector's cousin asks who wants another cheesedog and Travis turns to Hector and says, "You haven't had one dude" and Hector replies with, "I don't know. I just don't feel very hungry."
Maria, Ozzy and Drix are hiking trhough the wilderness and stumble upon the Appendix Lodge. They don't have any money, so in order to stay, they must work there: Maria as desk clerk and Ozzy and Drix as maids.
Hector and company are packing up camp. Hector moans and Travis asks him if he's still feeling bad, but Hector says he'll be okay. He then collapses on the ground with a moan. Everyone runs over and Hector says he's so sore. His cousin says, "You have a fever, but I think it's your appendix. We need to get him help before it ruptures!" Hector is in a lot of pain.
Maria is busy at the desk. Ozzy goes into a room as housekeeping, but realizes the occupant is still in the room.
Hector's cousin, Travis, and Jimmy are paddling to find help. Travis still can't get signal on his cell phone. Hector's cousin says, "Keep paddling. He's burning up!"
Drix's lugging a chest and takes a break when he realizes it's 102 degrees. He goes to talk to Billy Blog and learns about the roadblock.
Billy Blob is angry at his nephews for being away from guarding the sign. Billy Blob says a little heat never heat anybody.
Drix goes to tell Maria and Ozzy what's happening, but must get them to listen first. He tells what he knows. All of the germy guests could escape into the plasma rivers if the appendix explodes. They hear Hecton moan on the Eye Channel and Travis telling him to hang tough. They call a truce and must get rid of the detour sign and the guests. Maria and Ozzy take the sign, Drix the guests.
Hector and company hit some rough rapids, but make it through it. They congratulate themselves and Hector's getting delusional. Travis gets a signal on his cell phone.
Drix is handing out notices that guests must leave. Guests are leaving, but Billy Blob find out and keeps the guests at the lodge. Drix says they must shut down the lodge, but they all turn on him.
Ozzy and Maria find the detour. "Dumber and Dumbest" are guarding it. Ozzy disguises himself to relieve the men from the post, but they suspect something. Maria steps in disguises as a beautiful woman and they drool all over her. Maria tries to beat them up, but they're too big for her. Drix shows up and the men run, thinking its a bearasite.
Hector and company land, where a helicopter is waiting. Hector's onboard and his cousin tells him his mom will meet him at the hospital. The helicopter takes off.
Maria, Ozzy and Drix go to the Hoedown at the lodge. Ozzy tricks the germs into going outside, but Billy Blob intercepts and tells the germs to go after him. All three run with the germs chasing them. They get cornered.
Hector's arrived at the hospital and has anesthetics put into play so he can have surgery.
Ozzy, Drix and Maria, along with the germs, fall asleep due to the anesthetics. They wake up to find all the germs and the appendix gone.
Hector's in a hospital bed with his cousin, mom, Travis, and Jimmy around him. Travis and Jimmy want to see his stitches and Hector shows them after he's made him mom turn around.
Billy Blob is hitchhiking and Ozzy, Maria, and Drix pick him up, but he escapes on another car, but it's heading to the small intestines. Drix says it's a suitable ending.