CD52 is a GPI-anchored protein present in lymphocytes and male reproductive tissues (mrt) including mature sperm and seminal plasma. It has been shown that mrt-CD52 is synthesized in epithelial cells of the epididymis and vas deferens, but not in the testis. The mrt-CD52 is transported to mature sperm during sperm transition in the male reproductive tract. Lymphocyte CD52 functions to stimulate suppressor T cell induction, while mrt-CD52 is associated with seminogelin and involved in clot formation and liquefaction of semen. In a landmark study, a monoclonal antibody (Mab H6-3C4) from peripheral B lymphocytes of a patient with complement-dependent sperm-immobilizing antibody in the serum has been generated. Using Mab H6-3C4, the carbohydrate moiety of CD52 as an epitope for infertility-related antigen was identified. Mab H6-3C4 also shows strong complement-dependent sperm-immobilizing activity. This suggests CD52 may have a function in protecting sperm from complement activation. Indeed, purified mrt-CD52 from human sperm interferes with the classical pathway, but not lectin-binding or alternative pathways, of the complement systems. Recently, we found CD52 in ovulated cumulus cells from the female reproductive tissues (frt). The frt-CD52 is not recognized by Mab H6-3C4, suggesting that it harbors distinct carbohydrate antigenicity. Further studies are necessary to determine the molecular features and biological functions of CD52 in male and female reproductive tissues.