On a teacher conference day off from school, Bart and Milhouse decide to visit a joke shop. Meanwhile, Marge and Lisa plan a trip to the Springsonian Museum so they can see the Egyptian Treasures of Isis exhibit and the Orb of Isis. Marge has to take Bart to a doctor instead, since he has accidentally superglued various novelty items to his face. Since this is Lisa's last chance to see the exhibit, she phones Homer to ask him if she can take the bus. He seems uncertain, which prompts her to trick him into letting her take the bus.
Then, Lisa takes bus 22. Having not passed the museum for a long time, she asks the driver if the bus is bus 22. She learns that she is riding bus 22-A and is on the wrong bus. She has to get off at the last stop, which is in the middle of nowhere. During his lunch break at work, Homer has a conversation with Lenny and Carl. He tells them that he let Lisa ride the bus alone. Lenny and Carl point out the error of his judgment, and Homer leaves work to go look for her. He heads to the museum and ends up in downtown Springfield. He cannot find her in the large crowd of people. He buys a bunch of balloons and gives them to a city worker, so that he can use his cherrypicker to get up higher. Homer and Lisa spot each other, but the vehicle's wheels creak backwards and it rolls down a hill. After scraping his head under a tunnel and smashing into some traffic lights, it slides off the edge of a pier at the harbor into a river. Lisa tells the drawbridge operator to close the bridge so Homer can grab on. His head is caught between the two closing halves and he survives with nothing more than a few tire marks across his forehead.
Meanwhile, Bart's novelties get removed by Dr. Hibbert with "terror sweat". Marge and Bart return home, thinking Lisa is crying in her bedroom. Marge tells him to apologize to her, much to the anger of Bart. But, Bart hears no response from Lisa's empty room, thinking she is not talking to him. With Homer and Lisa re-united, he tells her that it is all right to take risks in life. The two decide to go to the museum after all, by illegally entering since it is now closed. While there, they make a fascinating discovery that the Orb of Isis is a music box which had gone overlooked by scientists and museum staff. Lisa concludes that what her father said about risks was right – until the alarm goes off and guard dogs chase them out of the building.