Antisperm antibodies can affect sperm function in the cervical mucus, as they undergo capacitation, or during sperm-egg interaction. During capacitation, the sperm membrane destabilizes and antigens previously not available to antibodies may become exposed. Antibody attachment can reduce fertilization as measured by hamster egg preparation or the hemizona assay. A panel of monoclonal and polyclonal patient sera were tested for their ability to inhibit sperm-zona pellucida tight binding. We tested 25 monoclonals from a panel from the World Health Organization, but only nine were positive by indirect bead binding, indicating that the majority of the antibodies were not sperm surface antigens. The sera of 13 patients were used; three were negative and served as controls, nine had antibodies of the IgG isotype bound to 100% of the sperm heads examined, and seven also exhibited sperm specific IgA antibodies. Of the monoclonals tested, six inhibited zona binding by 60%. Sera of seven patients caused inhibition of greater-than-or-equal-to 50% zona binding; those from male patients caused the greatest inhibition. When further specific testing was conducted, one monoclonal caused the greatest inhibition of zona binding; sera of three patients inhibited zona binding by 70%. The antibodies, whether monoclonal or patient sera, were tested for their effect on capacitation. The ability to undergo hyperactivated motility after antibody exposure was assessed and no changes appeared due to antibody exposure. Serum from one of the patients appeared to affect sperm calcium influx to some extent. Sera from two patients appeared to reduce the number of spermatozoa capable of undergoing the acrosome reaction. Antibody inhibition of binding was not due to agglutination or to steric hindrance, but to epitope specificity. These studies indicate that antisperm antibodies can affect sperm binding to the zona pellucida.