In CD-1 mice infected with Trypanosoma musculi, the production of IgM and IgG antibodies in response to sheep erythrocytes (SRBC) was significantly suppressed when mice were immunized with SRBC once high parasitaemias had developed. In infected mice which were not immunized with SRBC, background plaque-forming responses of spleen cells to SRBC were significantly higher than in uninfected, unimmunized mice. Factors derived from T. musculi were found to be mitogenic in vitro for spleen cells taken from CD-1 mice. The mitogenic response to these factors by spleen cells from athymic mice was highly significant, whereas the response of spleen cells taken from CD-1 mice which had been pre-treated with cyclophosphamide was much less, suggesting that the B cell was the major target of the trypanosome-derived mitogen. In this paper we discuss the possible relationship of T. musculi-induced mitogenesis to the immunosuppression and non-specific antibody formation associated with T. musculi infections.