Expression of mRNA of endothelin-1 (ET-1) and its receptors, endothelin receptor A (ET-A) and endothelin receptor B (ET-B), in human epididymis was assessed by reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry was performed on longitudinal sections through whole normal human epididymides. ET-1 mRNA was detested in caput, corpus and cauda epididymidis, Immunohistochemically, ET-1 was localized mainly in ciliated cells of efferent ducts and in some principal cells of epididymal duct. Larger arteries, but not epididymal microvasculature, contained ET-1 immunoreactivity. ET-A and ET-B mRNAs were detected in caput, corpus and cauda epididymidis. In efferent ducts, ET-A immunoreactivity was localized in ciliated cells. In the proximal region of the epididymal duct, ET-A immunostaining was localized mainly in basal cells whereas the distal region was devoid of ET-A immunoreactivity. Throughout the epididymis, blood vessels stained positive for ET-B. Furthermore. ET-B immunoreactivity was found in ciliated cells of efferent ducts and in basal cells of the distal epididymal duct. The fact that ciliated cells of efferent ducts contain ET-1 and both types of receptors indicates that ET-1 acts as an autocrine factor in these cells. ET-1 produced by efferent ducts and epididymal duct may control epididymal blood flow in a paracrine manner via ET-B receptors in epididymal blood vessels.