Two different BALB/c IgMk polyspecific monoclonal natural autoantibodies E7 and D23 were administered to neonatal BALB/c mice. When adults, these mice were immunized and challenged with calf myosin, BALB/c actin, human transferrin, calf thymus DNA or TNP-coupled bovine serum albumin (TNP/BSA), in complete Freund's adjuvant. The levels of serum antibody were evaluated by enzyme immunoassay. No differences in anti-actin, anti-transferrin and anti-DNA antibody titres were noted between control and antibody-treated mice. However, anti-myosin antibody titres significantly increased in mice treated with either the E7 or D23 antibody, and anti-TNP antibody titres significantly decreased in mice treated with E7 but not with D23. These differences persisted after antigenic challenge and involved only the IgG response of treated mice. These results suggest that polyspecific natural autoantibodies may be involved in the regulation of the humoral immune response.