Although autoimmune-prone mice bearing the lymphoproliferation (lpr) gene have polyclonally activated B cells and high serum titers of autoantibodies, they mount poor immune responses to exogenous antigens. In addition, they exhibit very low or nonexistent autologous mixed lymphocyte responses. Previous studies have shown that autoreactive T-cell clones have immunoregulatory properties: they can help suppress, or contrasuppress an immune response. Here we show that two autoreactive T-cell lines, GB4 and B1H1, can restore the defective response of C57Bl/6-lpr/lpr mice to the antigen sheep red blood cells. This restoration is antigen-dependent and requires the presence of other T cells.