The effects of the main male and female sex hormones, testosterones and estradiol, in pokeweed mitogen (PWM)-stimulated cultures of human blood lymphocytes were studied. We found that the addition of physiological concentrations of estradiol (780-2,600 pmol/liter) to PWM cultures significantly increased the accumulation of immunoglobulin M-containing and -secreting cells detected by immunofluorescence and/or by the reversed protein-A plaque assay. The dose range of estradiol that induced enhanced B cell maturation did not affect the proliferative response. Estradiol displayed the same effect in vitro on lymphocytes from both men and women. Fractionation of lymphocyte subpopulations before culturing revealed that estradiol does not display a direct mitogenic or stimulatory effect of B cells. Instead, estradiol inhibits the suppressive activity of a radio-sensitive (1,000 rad) subset of T lymphocytes bearing Fc-receptors for immunoglobulin G. Nontoxic concentrations fo testosterone did not influence the in vitro B cell maturation. These observations provide a cellular basis for the differences in the immunoreactivities of males and females. The estradiol-induced inhibiton of suppressor T cells might be important for the pathogenesis of various autoimmune disorders.