The innate resistance of the unnatural rat host to the mouse tapeworm Hymenolepis nana is cortisone sensitive but thymus independent. When congenitally athymic nude rats were orally given eggs, cysticercoids, or adult worms of H. nana, no lumenal adults were established except when they were treated with cortisone acetate during the expected lumenal development. The effect of cortisone to promote adult maturation in the rats was compared in nude and normal rats given eggs of H. nana. The fecundity of the worm (assessed by the fresh worm biomass and the number of infective eggs produced) was much higher in cortisone-treated nude rats than in cotrisone-trated norml rats. When the nude rats recostituted with thymocytes were given eggs and treated with cortisone, the fecundity of H. nana dropped to the same level as in cortisone-treated normal rats. It is strongly suggested that the unnatural rat host has thymus-independent cortisone sensitive resistance to an intial infection (which is the main component of the innate resistance and blocks the lumenal establishment of this parasite) and thymus-dependent resistance (which suppresses the established worm' fecudity and may be ascribed to acquired resistance to the ongoing infection).