Functions of carotid and aortic baroreflex control of heart rate (HR), cardiopulmonary baroreflex control of vascular resistance, adrenoreceptor responsiveness, indexes of baseline vagal and sympathetic tone, circulating blood volume, and venous compliance were compared in men and women to test the hypothesis that lower orthostatic tolerance in women would be associated with lower responsiveness of specific mechanisms of blood pressure regulation. HR, stroke volume (SV), cardiac output (Q), mean arterial blood pressure (MAP), central venous pressure, forearm (FVR) and leg (LVR) vascular resistance, catecholamines, and changes in leg volume (%DeltaLV) were measured during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 7 females and 10 males matched for age and fitness. LBNP tolerance for the women (797 +/- 63 mmHg/min) was 35% lower (P = 0.002) than 1,235 +/- 101 mmHg/min for the men. At presyncope, SV, Q, MAP, and %DeltaLV were lower (P < 0.05) in females compared with males, whereas HR, FVR, and total peripheral resistance were similar in both groups. Lower LBNP tolerance in females was associated with reduced HR response to carotid baroreceptor stimulation, lower baseline cardiac vagal activity, greater decline in Q induced by LBNP, increased beta1-adrenoreceptor responsiveness, greater vasoconstriction under equal LBNP, lower levels of circulating NE at presyncope, and lower relative blood volume. The results of this investigation support the hypothesis that women have less responsiveness in mechanisms that underlie blood pressure regulation under orthostatic challenge.