CD52 is a glycosylphosphatidylinositol (GPI)-anchored antigen expressed on lymphocytes and in epididymal epithelial cells. CD52 is also known as "maturation-associated sperm antigen" but its function is unknown. We therefore generated Cd52 disrupted mice. The resulting Cd52 null mice were healthy, even though Cd52 is expressed on cells of the immune system. We then examined a possible role for CD52 in reproduction. Sperm from Cd52-deficient males were investigated and the viability, motility, morphology, and incidence of spontaneous acrosome reactions were found to be all similar to values for wild-type sperm. In in vitro fertilization system, the sperm showed normal fertilizing ability. As CD52 was found to be transferred onto sperm only after they had migrated into the vas deferens, we examined the behavior of sperm from Cd52-deficient mice in vivo. The mice mated naturally and we observed that a normal number of sperm passed through the uterotubal junction, known to the crucial hurdle for various gene knockouts resulting in infertile sperm. As a consequence, there was no difference in the litter size from the wild-type and Cd52-null males. Our results therefore indicate CD52 is not required for fertilization in the mouse either in vivo or in vitro.