In this second Magic School Bus game based on the educational book series from Joanna Cole and Bruce Degen, Ms. Frizzle and her class take a trip inside classmate Arnold's body. From Arnold's head to his toe, the group travels through every system, including the Upper and Lower Digestive System, the Circulatory System, the Respiratory System, Liver, Nervous System and the skin. Only when all the areas and 12 body parts have been visited can the class leave Arnold's body through one of three natural exits.
All actions in this game are performed with the mouse. In the classroom, selecting the skeleton brings up a game of reassembling its bones; clicking on the science projects on the other side of the room trigger animations.
Once the bus is selected, the journey begins as the miniaturized vehicle zooms into Arnold's mouth. The player navigates through his body by clicking the steering wheel and selecting directional signs from the bus windshield; each place will lead to at least one other, and all lead to the nervous system from where any section can be visited. On the lower left sits Liz, the class mascot, who can be clicked for help. Clicking the rear view mirror takes the player to the back of the bus, where he can choose Tim's knapsack to access a drawing program, or Ralphie's handheld to play a game related to the current body part. As the player journeys through the body the places he has visited are recorded on a map in the glove box as well as stamped in a travel log, so he can see what has been missed. Unlike later Magic School Bus games, the player is unable to exit the bus, all the action takes place inside and in the classroom.