Incidence and characterization of antibodies to zona pellucida (Z.P.) in human sera were studied and the following results were obtained. Some human sera showed positive immunofluorescent staining of porcine Z.P. after absorption with porcine red blood cells, liver and kidney. The incidence of immunofluorescence positive sera in infertile women was not significantly different from pregnant women and healthy men after absorption with porcine red blood cells, liver and kidney. Among sixteen sera with positive staining of porcine Z.P. after absorption, only two showed positive staining of human oocytes. The gammaglobulin fraction from the above two sera also stained human Z.P. but neither precipitated on the surface of Z.P. nor blocked human spermatozoa to penetrate into Z.P. of human oocytes. There was no correlation between the incidences of antibody to porcine Z.P. and of sperm immobilizing antibody in human sera. Some human sera blocked monoclonal antibodies to porcine Z.P. with different specificities to bind the solubilized porcine Z.P. antigens in an enzyme linked immunosorbent assay. The incidences of the positive sera were not significantly different among the groups of infertile women, pregnant women and healthy men. These results clearly indicate that anti Z.P. antibodies detected by the immunofluorescent staining of porcine Z.P. had no correlation with infertility. The presence of such antibodies, even in the sera of men, suggests that they might be the antibodies produced to some foreign antigens cross-reactive to porcine Z. P. but not autoantibodies produced to human Z.P.