The immune response of rats to infection with Trichinella spiralis was studied serially for more than 1 year. Initial antigen-specific cellular reactivity, assessed by the lymphocyte transformation response, developed in the draining mesenteric nodes 3 days after infection. After 1 week reactive lymphocytes were detectable in the spleen and circulating blood, but the more ‘remote’ peripheral nodes did not harbor antigen-reactive cells until late in the second week. Thereafter, the patterns of antigen-responsiveness varied among the different lymphoid pools, but in all cases a decline in reactivity was seen after the first month. Serum hemagglutinating and homocytotropic antibodies, detectable by the tenth day, reached their peaks after 1 month of infection. Hemagglutinating titers persisted for more than 1 year but homocytotropic antibody was lost over this period. Comparisons are drawn between the evolution of the natural infection and the development of the host’s immune response.