Most studies of the reflex responses to cardiopulmonary baroreceptor unloading with lower body negative pressure (LBNP) have assessed responses during the first few minutes of LBNP. It is unknown if these early changes are representative of the steady state. Thus we determined the response of heart rate, arterial pressure, forearm vascular resistance (FVR), and plasma norepinephrine (NE), renin (PRA), and aldosterone to prolonged (20 min) LBNP in nine normal subjects. All measurements were obtained at base line and after 3, 10, and 20 min of LBNP (-10, -20, and -40 mmHg). A 20-min recovery period was interposed between each period of LBNP. The heart rate and mean arterial pressure responses to LBNP during all levels of suction were not significantly different at 3, 10, and 20 min of continuous suction. Changes in FVR at 3, 10, and 20 min, respectively, were 18.4 +/- 3.2, 26.3 +/- 4.2, and 19.6 +/- 4.2 U during LBNP -10 mmHg; 33 +/- 7, 30.5 +/- 7.6, and 30 +/- 5.2 U during LBNP -20 mmHg; and 53.6 +/- 11.7, 57 +/- 8.8, and 49.4 +/- 12 during LBNP -40 mmHg, thus indicating a near maximal vasoconstrictor response at 3 min that was sustained throughout the 20 min during all levels of LBNP. Plasma NE rose to near peak level by 3 min. However, PRA and aldosterone changed significantly only after 20 min during LBNP at -10 and -20 mmHg. These data indicate that LBNP activates the sympathetic nervous system early, whereas activation of the renin-angiotensin-aldosterone axis is delayed. Our data should be taken into consideration in the design of future investigations of reflex neurohumoral responses to LBNP.