OBJECTIVE Research studies in animal and human systems have demonstrated conclusively that antisperm antibodies can interfere with fertilization. In the male, autoantibodies to sperm can be detected both in the sera and seminal plasma. METHODS Ninety-seven men who were tested for antisperm antibodies as a part of an infertility evaluation were identified. Complete medical history was obtained, including information related to events suspected of being associated with antisperm antibodies. History of surgery (varicocele repair, hernia repair, and vas reversal) and infection (epididymitis, sexually transmitted disease, and orchitis) were compared with semen parameters (motility less than 60%, concentration less than 20 x 10(6), and volume less than 2 cc). These were compared to antisperm antibody results of mixed agglutination reaction (MAR) and direct immunobead binding test (IBT) for immunoglobulin G (IgG). Statistical analysis was performed using Fishers exact two-tailed test. RESULTS As expected, prior vas reversal was significantly associated with the presence of antisperm antibodies (P = 0.0002) by MAR or IBT with a fivefold increased relative risk (95% confidence interval, 1.97-12.38). Other surgeries manipulating the cord structures independent of vas reversal were not associated with antisperm antibodies (P = 0.09). Prior infections, independent of vas reversal, were significantly associated with antisperm antibodies by MAR (P = 0.04) with a 3.8-fold increased relative risk (95% confidence interval, 1.06-13.87) but not by IBT. Sperm concentration less than 20 x 10(6), motility less than 60%, and a volume less than 2 cc were not associated with antisperm antibodies by MAR or IBT. CONCLUSIONS These findings suggest that manipulation of the cord structures excluding the vas were not associated with antisperm antibodies; however, vas reversal and prior infection are significant risk factors for the development of antisperm antibodies.