Erythrocyte autoantibodies can be elicited in mnce by injections of rat RBC which are cross-reactive with mouse RBC. This report shows that induction of autoantibodies is dependent, in part, on gene(s) outside the H-2 complex. Using CBA mice congenic for Ig allotype and the F1 and F2 hybrids, a higher incidence of autoantibody production was observed in mice bearing the Ig allotype 1b (1b/b or 1a/b) in contrast to mice homozygous for the allotype Ig-1a. Serum haemagglutination titres against rat RBC were not reduced in the groups of mice with the lower incidence of autoantibody production. A probable explanation for these observations is that the change in Ig allotype is associated with some change in the variable region determining autoimmune specificity that is governed by VH genes linked to allotype genes. The transfer of 30 x 10(6) spleen cells from Coombs' positive mice to syngeneic recipients before starting the immunization regime with rat RBC suppressed autoantibody production and enhanced antibody production against rat RBC. These suppressor cells were effective in congenic mice and in F1 hybrids, which suggest that the Ig allotype is not a crucial site for the effector stage of suppression of this autoimmune response.