Oxytocin (OT) is a neurohypophysial hormone with overall unclear physiological functions in the male. Several studies indicated that OT has a key role in the central regulation of penile erection. In this mini-review we summarize its possible involvement in another aspect of the male sexuality: the ejaculatory process. Because OT is released by posterior pituitary at the time of orgasm, we postulate that OT might help sperm progression during ejaculation. Our recent studies indicate that OT receptors (OTR) are present in rabbit and human epididymis and mediate contractility. Accordingly, they are immuno-localized in the smooth muscle cells of the epididymis. However, they are also present in the epithelial compartment of the tubules. In epididymal epithelial cells in culture, OT induces the release of another potent stimulator of epididymal contractility, endothelin-1 (ET-1), which most probably amplifies OT-induced contraction. Sex steroids regulate the density of OTR in epididymis. In fact, in an experimental model of hypogonadotropic hypogonadism (hypo) induced in rabbits, estrogens, but not androgens, fully restored OT-induced epididymal contractility, up-regulating OTR gene and protein expression. In addition, deprivation of endogenous estrogens, by blocking their formation using the aromatase inhibitor letrozole, induced OT hypo-responsiveness comparable to that observed in hypo rabbits. These findings suggest a new function of estrogens in the male: regulation of OT responsiveness in epididymis.