The effect of Trypanosoma brucei infections on parasite-specific antibody responses was examined by immunization of infected mice with radio-attenuated trypanosomes of a noncross-reacting clone. Antibody titers (total Ig) against variant surface antigen were determined by indirect immunofluorescence. The suppression resulting from acute infection was virtually complete, and is associated with the failure to control the first relapse variant of the acute clone. The suppression resulting from chronic infection was much less severe, and subsequently variant populations of the chronic clone are successfully controlled. Antibody collected 10 days after each of the first 3 peaks of parasitemia during chronic infection was titrated on the homologous parasite preparations isolated from each wave in individual mice. As the infection progressed, both IgG and IgM antibody responses to each successive wave declined However, the decline of IgG antibody was more rapid than IgM, so that by the third parasite wave the mice responding with predominantly, if not exclusively, low levels of IgM antibody. We conclude that the severity of trypanosome-induced suppression of the anti-parasite response and IgM response in particular, determines the course of infection by trypanosomes varying in virulence.