A comparison was made of the immunological responses of inbred NIH mice to the intestinal stage of infection with two species of the genus Trichinella, T. spiralis and T. pseudospiralis, which are known to have distinct parasitological and pathological relationships with their hosts. The parameters studied, namely antigen-specific IgG1 and IgG2a antibody responses, mucosal mastocytosis, and levels of the cytokines interferon-gamma (IFN-gamma) and interleukin-5 (IL-5) produced by concanavalin A-pulsed mesenteric node lymphocytes in vitro, were chosen to provide information about the relative activities of the Th1 and Th2 T-helper (Th) lymphocyte subsets. In this high-responder host the time-course of infections was similar, although initial levels of establishment were considerably higher for T. pseudospiralis. Both species elicited mucosal mastocytosis. Distinct differences were seen in the IgG isotype responses. Trichinella spiralis-infected mice produced a predominantly IgG2a response, whereas T. pseudospiralis elicited an IgG1 response. Cytokine release showed infection dose-related suppression of IFN-gamma and enhancement of IL-5. These effects were most marked in T. pseudospiralis-infected mice, i.e. there was an earlier shut-off of IFN-gamma and an earlier switch to IL-5. These data suggest that the two species of Trichinella show a time-related differential activity of Th subsets during the early stages of infection. The possibility that this may reflect antigenic differences between these closely related species or result from parasite-induced immunological-endocrinological changes is discussed.