OBJECTIVE To determine the effects of PRL suppression on the activation of murine peritoneal macrophages and their subsequent effects on human sperm motility. METHODS Laboratory study. METHODS Mice were treated with subcutaneous implants of 2.5 mg bromocriptine pellets 7 days before bacillus of calmette and guerin (BCG), a strain of Mycobacterium bovis, injection for activation of macrophages. Bromocriptine treatment, which significantly suppressed circulating PRL levels, continued through the day of peritoneal macrophage collection. Macrophages were subsequently cultured for 4 days and culture supernatant was collected. METHODS Human sperm were incubated for 4 hours in the presence of culture medium or culture supernatant from control and treated mice. Motion analysis was performed at 0, 2, and 4 hours. RESULTS A significant decrease in human sperm motility was observed in the presence of culture supernatant from activated murine peritoneal macrophages. After 4 hours of incubation, sperm motility decreased from 69% +/- 3% in the nonactivated macrophage control group to 37% +/- 6% in the BCG- activated macrophage group. The suppressive effect of soluble products of activated macrophages on human sperm motility was reversed when mice were rendered hypoprolactinemic with bromocriptine. Motility after 4 hours was 56% +/- 3% in the BCG-bromocriptine group. Simultaneous administration of bromocriptine and PRL (100 ng per mouse daily) restored the inhibitory effect of soluble products of activated macrophages on sperm motility (36% +/- 5% motile). CONCLUSIONS PRL may modulate the deleterious effects of activated macrophages on human sperm motility, thereby suggesting novel and useful methods for the modification of the immune response in early reproduction.