To elucidate relevance of estrogens to immune responses, we investigated whether estrogen receptor alpha (ERalpha) exists in mouse splenic B cells and T cells and the effect of 17beta-estradiol and endocrine disrupting chemicals (EDCs) on lymphocyte mitogenesis. ERalpha was identified in both male and female mouse splenic cells using RT-PCR. Crude splenic cells were stained with anti-ER antibody, and the distribution of ERalpha in the splenic B cells and part of the splenic T cells was confirmed by flow cytometry. 17beta-Estradiol inhibited B cell mitogenesis at the concentration of 10(-8) M and T cell mitogenesis at the concentration of 10(-6) M. Some EDCs, diethylstilbestrol, bisphenol A, p-nonylphenol and di-2-ethylhexylphthalate, suppressed lymphocyte mitogenesis at the concentration of 10(-6)-10(-5) M. We therefore suggest that estrogen may suppress lymphocyte mitogenesis through ERalpha in B and T cells.