Cultured peritoneal cells from untreated mice, after 3 days of in vitro culture, produce autoantibodies against bromelain-treated isologous erythrocytes. The autoantibody response varies with both age and gender. The effects of age and gender were demonstrated by culturing peritoneal cells using limiting dilution techniques. In neonatal mice there were no precursor cells that differentiated into autoantibody secretors. Cells from female mice gave higher responses than cells from males, and the effect was more pronounced in cells from older mice and cultures to which lipopolysaccharide/dextran sulfate (LPS/DS) had been added. Various cell separation and cell mixing experiments indicated that a non-B-cell, nonadherent cell was involved in the higher autoimmunity detected in the presence of LPS/DS in female and older mice. It is thus possible that low autoimmune responses are due to the absence or unresponsiveness of accessory cells rather than potentially autoimmune B-cells.