CD52 is the product of a single gene on chromosome 1, first characterized as a human leukocyte differentiation antigen expressed on the surface of lymphocytes and monocytes and then identified in the epithelial cells of epididymal corpus and cauda and in the deferent ducts. Sperm also have this antigen, acquiring it as they pass through the epididymis. The precursor of CD52 is 61 amino acids long, but the mature antigen, that serves as backbone for N-glycosylation and a final GPI-anchor, only contains 12 amino acids.           O-linked oligosaccharide chains are also bound to certain glycoforms of this complex antigen. The first and most commonly used anti-CD52 monoclonal antibody, termed CAMPATH-1, generated in the immune system, interacts with the last three amino acids and the first part of GPI, and recognizes CD52 on leukocytes, epididymal cells and sperm. Other antibodies such as S19 and Mab H6-3C4 react only with CD52 carbohydrate epitopes specific to the reproductive system. We generated a polyclonal antibody that mainly recognizes CD52 glycoforms containing O-linked oligosaccharide chains. We called this antibody anti-gp20 because it was raised against a 20 kDa sialylglycoprotein, homologous to CD52, recovered as sole radiolabelled glycoprotein after radiolabelling surface sialic acid residues of capacitated human sperm. Anti-gp20 revealed that the O-glycan-containing glycoform in capacitated sperm differs from the other CD52 glycoforms in localization on the surface and microdomain segregation. This does not occur on leukocytes and freshly ejaculated sperm. Since this form specifically localizes in the equatorial region of sperm capacitated in vitro and anti-gp20 impairs sperm penetration of denuded hamster eggs, a role in sperm-egg fusion has been suggested for it. The capacity of CD52 to form a complex with semenogelin I recently indicated that the antigen also has a role in semen clot formation and liquefaction.