The effects of purified human sperm fertilization antigen-1 (FA-1), affinity-purified monoclonal Fab' antibody to FA-1, and monoclonal Fab' antibody to phosphotyrosine residues on human sperm-zona interaction were investigated. The purified FA-1 antigen completely blocked sperm binding to zona pellucida (P < 0.0001). Also, the monoclonal Fab' antibodies to FA-1 antigen and phosphotyrosine residues significantly (P < 0.05) reduced sperm-zona pellucidae and the antibodies were preincubated with sperm before insemination and not vice versa. These results suggest that the tyrosine phosphorylation especially of FA-1 antigen has an important role in zona pellucida receptor recognition and binding. These findings also suggest that FA-1 antigen may be the sperm receptor involved in zona pellucida binding in humans.