Antibody responses were evaluated in inbred mice previously shown to be susceptible (A/J) or resistant (C57BL/6J and B6AF1 hybrid) to infections with relatively avirulent Trypanosoma congolense. Titres and the isotype distribution antibodies specific for the trypanosome variant surface glycoprotein (VSG) were determined by indirect immunofluorescence in sera of mice after primary infections with Trypanosoma congolense and after challenge infections with the same variant following drug cure. The results of these investigations showed that, during active infection, resistant mice made relatively strong VSG-specific IgM antibodies. This isotype also predominated in challenge infections with the homologous variant following drug cure. In contrast, A/J mice made little or no VSG-specific antibody on first exposure to T. congolense. However, these animals were able to produce substantial amounts of protective VSG-specific IgG antibody after multiple-challenge infections with the homologous variant. Substantial titres of VSG-specific antibodies in resistant mice did not influence the numbers of trypanosomes in the first parasitaemic peak as initial parastiaemias were similar in both C57BL/6J and A/J mice. However, C57BL/6J mice cleared parasites in this peak, whereas A/J mice did not. Mice of both strains immunized by infection cure were equally effective in clearing parasites when challenged with homologous trypanosomes. It is clear from the results of this study that antibody is not the sole factor contributing to murine resistance to African trypanosomes.