Intravenous administration of cimetidine, a histamine (H2) receptor antagonist, provoked an immediate 2 to 3-fold rise in serum prolactin concentrations in 8 normal men; serum thyrotropin, growth hormone, thyroxine, and triiodothyronine were not significantly affected. Diphenhydramine, an H1-antagonist, was without effect on any of the hormones measured. The results suggest that histamine may have an important function in the regulation of prolactin secretion in man.