When BALB/c mice initially given cysticercoids of Hymenolepis diminuta orally (Day 0) were challenged with eggs or cysticercoids of H. nana, almost all the mice became completely resistant to H. nana challenges from Day 30 onward, and no luminal adults of H. nana were established. There was a tendency for the number of tissue cysticercoids recovered 4 days after egg challenge in immunized mice to be much less than that in control mice (P less than 0.001, Student's t test). However, when these cysticercoids recovered from immune group mice were inoculated into uninfected mice, they matured in the lumen. Thus, the cross immunity to H. nana challenge evoked by an initial prepatent infection with H. diminuta appeared to be directed not against the tissue phase but against the lumen phase of H. nana. When BALB/c mice initially given eggs of H. nana were challenged with H. diminuta, they became resistant to H. diminuta from Day 15 onward. When the mice given eggs of H. nana were treated with a cestocide, praziquantel, at the beginning of the expected luminal development of H. nana and experienced a tissue phase only before challenge with H. diminuta, they showed no resistance to H. diminuta. Thus, the cross immunity to H. diminuta challenge evoked by an initial patent infection with H. nana appeared to be due to the immunogens of the lumen phase of H. nana but not those of the tissue phase. The cross immunity may be, therefore, essentially evoked by the lumen phase of these two phylogenetically closely related species and not by or against the tissue phase of H. nana.(ABSTRACT TRUNCATED AT 250 WORDS)