In an abandoned river boat in Devil's Bayou, Louisiana, a young orphan named Penny drops a message in a bottle, containing a plea for help, into the river. The bottle washes up in New York City, where it is found by the Rescue Aid Society, an international mouse organization inside the United Nations. The Hungarian representative, Miss Bianca, volunteers to accept the case and chooses Bernard, a stammering janitor, as her co-agent. The two visit Morningside Orphanage, where Penny lived, and meet an old cat named Rufus. He tells them about a woman named Madame Medusa who once tried to lure Penny into her car and may have succeeded in abducting Penny this time.