We have previously documented an inverse relationship between serum levels of anti-F(ab')2 antibodies and disease activity in systemic lupus erythematosus (SLE). The present study focused on the specific in vitro inhibition of anti-DNA producing cells from SLE patients by autologous anti-F(ab')2 antibodies. Peripheral blood lymphocytes (PBL) from eleven inactive SLE patients with no apparent disease activity were cultured in vitro to evaluate anti-DNA antibody secretion. Low levels of synthesis of anti-DNA antibody were detected in 3 of 11 SLE patients using unstimulated PBL; on the contrary, pokeweed mitogen stimulation of cultured cells increased production of anti-DNA in all SLE subjects. Parallel cultures were also performed in the presence of heterologous and autologous anti-F(ab')2 antibodies and results on production of anti-DNA evaluated. Lymphocytes from SLE patients in remission showed inhibition of synthesis of anti-DNA antibodies when autologous anti-F(ab')2 antibodies were added to the cultures, whereas production of anti-tetanus toxoid IgG by the same cells was not significantly altered under the same conditions. These data suggest that a functional anti-idiotypic role may be assigned to anti-F(ab')2 antibodies during clinical remission of SLE.