Human preimplantation embryos, gametes and cumulus cells were studied for expression of the complement-binding proteins CD46 (membrane cofactor protein), CD55 (decay accelerating factor) and CD59 (membrane attack complex inhibitory factor) as well as complement receptors type 1 (CRI), type 2 (CR2) and type 3 (CR3). Both the CD55 and CD59 glycosyl phosphatidylinositol (GPI)-anchored proteins were expressed by the plasma membrane and zona pellucida of oocytes, early embryos and expanded preimplantation blastocysts; in contrast, CD46 was expressed only on the plasma membrane. Cumulus cells consistently expressed CD46 and, most strongly, CD59 whereas CD55 expression was variable. Monoclonal antibodies (mAbs) to CRI, CR2 and CR3 epitopes gave only occasional reactivity on oocytes and were unreactive with blastocysts, spermatozoa and cumulus cells. CD46 is expressed only on the spermatozoal inner acrosomal membrane, and CD59 on the plasma membrane; CD55 expression was confirmed on the plasma membrane as well as the inner acrosomal membrane. Control mAbs specific for factor H were usually unreactive with gametes, blastocysts and cumulus cells. These data support the concept that gametes and early embryonic cells are protected from complement-mediated attack by expression of CD46, CD55 and CD59, although these complement-binding proteins may have additional roles in reproductive events.