The ability to induce autoantibodies to erythrocytes in male and female (NZB x NZW)F1 mice was examined. Female (NZB x NZW)F1 mice were shown to produce significantly more autoantibody than the male (NZB x NZW)F1 mice. The regulation of this experimentaly induced autoantibody was studied by examining the ability of male and female (NZB x NZW)F1 mice to generate antigen-specific suppressor cells. A sex difference was found in the ability to generate these suppressor cells. Male mice generated antigen-specific suppressor cells in response to rat RBC which were capable to suppressing the experimental induction of red cell autoantibodies whereas female mice were unable to generate those antigen-specific suppressor cells.