Responsiveness of mouse strains after phase-specific immunization with Trichinella spiralis is compared. Two strains (NFR/N, NFS/N) showed strong overall responsiveness. The response type could be characterized in phase-specific terms as strongly anti-adult, weakly to moderately anti-preadult and strongly antifecundity. By comparison, congenic mice of the C57B1 10/Sn background (B10 .cntdot. A, B10 .cntdot. D2, B10 .cntdot. S, B10 .cntdot. Q) displayed poor total responses that could be characterized as weakly anti-adult, very weakly anti-preadult, weakly anti-fecundity after preadult immunization and mixed (weak and strong) after adult immunization. The C3H/HeJ mouse appeared to be intermediate between the B10 .cntdot. BR and the NFR/N strains in overall responsiveness. Genetic determinants of anti-preadult or anti-adult responses of NFR/N strain mice were dominant over their B10 congenic counterparts as shown in F1 crosses of NFR/N .times. B10 .cntdot. BR mice. The NFR/N (predominantly H-2q) and the NFS/N (H-2s) are both strong responders, while the B10 .cntdot. Q(H-2q) and B10 .cntdot. S (H-2s) are weak. Apparently, the major genes controlling anti-preadult and anti-adult responses are not linked to the major histocompatibility [MHC] complex. Variations in anti-adult immunity and anti-fecundity in the B10 congenic mice (B10 .cntdot. Q and B10 .cntdot. S are the strongest responders) suggest minor genes linked to the MHC exert some control over these responses. Some evidence was obtained for gene complementation as the F1 cross of NFR/N and NFS/N mice responded more vigorously than the parental lines. Apparently, multiple genes determine anti-T. spiralis intestinal responses in mice. The major genes are unlinked to the MHC whereas several minor genes are linked.