The mouse in vitro fertilization system was used to investigate the effect of human seminal plasma (HSP) on the fertilizing ability of mouse spermatozoa. The addition of HSP to freshly collected mouse epididymal spermatozoa decreased their fertilizing ability to 30%, compared with 85-90% for control spermatozoa not exposed to HSP or for spermatozoa that had been exposed to the capacitating system for 55-145 min (which allowed capacitation to occur before the addition of HSP). Human seminal plasma from a vasectomized donor was more effective in retarding the acquisition of fertilizing ability in mouse spermatozoa than was seminal plasma from non-vasectomized donors. Fluid from the prostate glands and seminal vesicles of mice also reduced the fertilizing ability of freshly collected mouse spermatozoa to 30%.