Estrogen receptor mRNA expression was detected in the head and tail parts of the human epididymis by means of reverse transcription polymerase chain reaction (RT-PCR). Immunocytochemical labelling showed that ciliate and nonciliate cells from the epithelium of the efferent ductules possessed strong to moderate nuclear staining for estrogen and progesterone receptors. The epididymal duct was negative for both antigens. Vascular endothelial cells also showed estrogen receptor, but no progesterone receptor immunolabelling in all regions of the organ. Immunoreactivity for the estrogen receptor-related antigen (ER-D5) was seen in the cytoplasm of ciliated and nonciliated epithelial cells from the efferent ductules, in the basal cells of some epididymal duct profiles as well as in myofibroblasts of the lamina propria, endothelial cells and smooth muscle cells of the vessel walls. The results obtained suggest that the epithelial cells of the efferent ductules of the human epididymis may be main target structures of estrogens and progestins.