The effect of reserpine at various concentrations (2 X 10(-6), 2 X 10(-7), 2 X 10(-8), 2 X 10(-9) and 2 X 10(-10) M) on the in vitro fertilizing capacity of human spermatozoa was studied. Spermatozoa collected from presumably fertile men were washed in BWW medium and incubated with different concentrations of reserpine for 5 hr before insemination of the zona-free hamster ova. The spermatozoal penetration of the zona-free hamster ova was scored 6 hr later and the results were analyzed statistically. Reserpine, at all the concentrations tested, caused a significant dose-dependent decrease in the penetration of the denuded hamster ova in comparison to the control (p less than 0.05). The percent motility of spermatozoa decreased as a function of time during the preincubation period to initiate spermatozoal capacitation but there were no significant differences in the values between the control and the reserpine - treated spermatozoa (p greater than 0.05). These findings indicate that reserpine can affect the fertilizing capacity of human spermatozoa in vitro and provide an additional evidence to suggest the prospective use of reserpine as a vaginal contraceptive.