Gender appears to influence systemic and organ-specific inflammatory sequelae of ischemia-reperfusion and infectious challenge in many animal models. Despite the protection provided by female gender, androgen blockade, and/or estrogen administration in such experimental studies, many questions remain regarding the influence of gender dimorphism upon human responses to injury. We hypothesized that the administration of low-dose lipopolysaccharide (LPS) to otherwise healthy, young adults would provide insights regarding the influence of gender upon physiological and innate immune system responses to a prototypic inflammatory stimulus. To this end, 72 adult subjects (48 men, aged 29 +/- 1.0 years; 24 women, aged 26 +/- 1.0 years) were prospectively evaluated before and after the i.v. administration of LPS (2 ng/kg). All subjects developed symptoms within 1.0 to 1.5 h after LPS, and the men exhibited a greater increase in core temperature (2.1 +/- 0.1 degrees C) compared with the women (1.4 +/- 0.1 degrees C) (P < 0.001). In addition, the men exhibited a greater maximum decrease in mean arterial pressure (-13.0 +/- 1.3 mmHg) compared with the women (-8 +/- 1.3 mmHg) (P < 0.02). The changes in temperature and mean arterial pressure occurred without detectable differences between the male and female cohort responses of circulating white blood cell count and cortisol or cytokine levels. These results suggest that soluble inflammatory mediators generated by in vivo endotoxin activation of the innate immune system are insufficient to explain the resultant gender-specific phenotypic differences observed in young, adult humans.