Life has been hard for Mrs. Frisby ever since her husband died. When her youngest son becomes dangerously ill and needs to be moved in order to avoid the farmer's plough, she doesn't know what to do. A wise owl advises her to ask the rats for help, but Mrs. Frisby is hesitant—how could a rat help her?

Then she learns a surprising truth. Not only did the rats know her husband well, but they also shared a secret with him. They were all once laboratory captives, subject to injections and tests, which made them more cunning than ordinary animals. In fact, the rats have built an underground city, full of secret passageways and great machines! They agree to help Mrs. Frisby—but when the farmer calls for exterminators to take care of his rat problem, the rats may need more help than one little mouse can give in return.