Although factors influencing renin release have been studied extensively, one facet of renin release remains controversial, namely, neural regulation by arterial high-pressure receptors and cardiopulmonary low-pressure receptors. We therefore designed four studies to investigate systematically the separate and combined effects of unloading (decreased stretch) high- and low-pressure receptors on renin release in normal men. Selective unloading of cardiopulmonary receptors was induced by impeding the venous return with tourniquets around the thighs. A predominant unloading of arterial (carotid) baroreceptors was elicited with upright posture and simultaneously preventing the venous pooling in the legs. Unloading of both high- and low-pressure receptors was achieved by both upright standing and tilting. During postural experiments to predominantly unload arterial baroreceptors, the heart rate increased and the veins constricted, but renin failed to increase. The postural increase of renin occurred only if we allowed venous pooling in the legs. Selective unloading of cardiopulmonary receptors elicited substantial increases of renin. When both the cardiopulmonary and arterial baroreceptors were unloaded, renin increased more than with isolated unloading of cardiopulmonary receptors. We conclude that: 1) in intact humans it is possible to demonstrate an independent role of cardiopulmonary receptors in the control of renin release; 2) there Is evidence for interaction between the two receptor systems in renin control; but 3) an independent role for arterial baroreceptors in the control of renin release could not be demonstrated under the conditions of this experiment.