A bottle containing a plea for help arrives at the Rescue Aid Society, an organization of mice from all over the world whose mission is to help those in need. Bernard and Miss Bianca are chosen for the task and after gathering the needed clues and information, they fly on the back of albatross Orville to the gloomy and uncharted Devil's Bayou. There, together with Ellie Mae and other swamp folk, they must work together to save a little orphan girl from the evil Madame Medusa.
