Studies of the effect of sex hormones on the susceptibility of mice to the disseminated gonococcal infection demonstrated significantly enhanced susceptibility of mice injected with estrogen (17 beta-estradiol). In mice treated with estradiol, bacteremia progressively developed within 12 h postinoculation and mice died within the next 6 h, whereas bacteremia in mice treated with progesterone was completely cleared within 3 h postinoculation. The administration of estradiol affected the function of polymorphonuclear leukocytes (PMN) responsible for eliminating gonococci, but the administration of progesterone did not. The bactericidal activity of PMN mediated by myeloperoxidase was affected by estradiol, but the capacity of PMN to release superoxide anion was not. Furthermore, peritoneal cell analysis demonstrated that the infiltration of PMN in the peritoneal cavity of estradiol-treated mice significantly decreased when mice were injected intraperitoneally with gonococci. These effects on PMN by estradiol may play an important role in the enhanced susceptibility of estradiol-treated mice to gonococcal infection.