To test the hypothesis that unloading cardiopulmonary receptors improves human carotid baroreceptor responsiveness we measured heart rate (HR) and mean radial artery blood pressure (BP) responses elicited by trains of neck pressure and neck suction from +40 to -65 Torr during graded lower body negative pressure (LBNP) at -5, -10, -15, -20, -35, and -50 Torr in eight healthy men. Gain of the carotid baroreflexes was determined from logistic modeling of the HR [expressed as R-R interval (RRI)] and BP responses to neck pressure and neck suction. Central venous pressure (CVP) decreased progressively from control values of 6.2 +/- 0.6 (SE) Torr to -0.8 +/- 0.1 Torr at -50 Torr LBNP (P less than 0.001). HR changed little from control values of 62.7 +/- 2.1 beat/min to 65.9 +/- 2.8 beat/min at -15 Torr (P = NS), but increased significantly to 80.6 +/- 2.6 beats/min at -50 Torr (P less than 0.001). Maximum gain of the HR and BP stimulus-response curves was linearly and inversely related to decreases in CVP and could be described by the relationships Max RRI gain = -0.694 (CVP) + 11.6 [r2 = 0.94, standard error of estimate (SEE) = 0.45, P less than 0.001] and Max BP gain = -0.0292 (CVP) + 0.391 (r2 = 0.81, SEE = 0.038, P less than 0.001). We suggest that reductions in central venous pressure and/or central blood volume augment both HR and BP carotid baroreflex responses in man by reducing an inhibitory influence from cardiopulmonary receptors.