Testosterone and estrogen are hormones important to both sexes. In the adult testis, estrogen is synthesized by Leydig cells and germ cells, producing a relatively high concentration in rete testis fluid and in semen of several species. Estrogen receptors (ER) are present in the testis, efferent ductules and epididymis of most species; however, ERα is reported absent in the testis of a few, including man. ERα is abundant in the efferent ductule epithelium of every species examined to date. Its primary function is the regulated expression of proteins involved in fluid reabsorption. Disruption of ERα, either in the knockout (ERαKO) or by treatment with a pure antiestrogen, results in dilution of cauda epididymal sperm, disruption of sperm morphology, inhibition of sodium transport and subsequent water reabsorption, increased secretion of Cl- , and eventual decreased fertility. Loss of aromatase activity in the ArKO mouse does not result in an ERαKO or antiestrogen phenotype, suggesting that epithelial ERα in the efferent ductules may exhibit ligand-independent activity. In addition to the primary regulation of luminal fluid and ion transport, estrogen is also responsible for maintaining a differentiated epithelial morphology through a mechanism remaining to be discovered. Thus, estrogen or its receptor is important for male reproductive tract function in numerous species