Immune responses to unrelated antigens were studied during the course of Trichinella spiralis infection in mice. A transitory depression of the IgM response to the thymus dependent antigen, sheep erythrocytes, was seen three weeks after infection and this effect was more pronounced after challenge. A depression of the IgG response also was observed, however, not until 6 weeks after infection. The humoral response to the thymus independent antigen, polyvinyl pyrrolidone showed a slight increase which was most evident in challenged mice. The nonspecific cellular immune response, as measured by the split heart allograft technique, showed a profound and longlasting depression. This effect was mot pronounced one week after inoculation, when the parasite resides mainly in the intestine. The time at which the nonspecific cellular immunity was most depressed coincides with the period of strong specific cell mediated immunity. It is also shown that experimental trichinosis in CBA mice is accompanied by profound but transient changes in the thymus reflected mainly as a depletion of cortical thymocytes. These changes were not due to corticosteroids or malnutrition. There is reason to believe that thymic depletion is of significance for the depressed antibody response, but not for the prolonged survival of allografts. These findings indicate that T. spiralis affects the nonspecific immunity at different levels.