During static exercise, several reflex systems that increase sympathetic nerve activity, heart rate, arterial pressure, and cardiac output are activated. At rest, the renal circulation receives the most blood flow per tissue weight of any organ in the body. However, the renal circulatory response to static exercise has not been studied in humans because of technical limitations in methods for measuring rapid changes in renal blood flow. The aim of this study was to determine the renal blood flow response to static exercise in healthy humans and, specifically, to clarify the reflex mechanisms underlying this response. Renal cortical blood flow was measured using dynamic positron emission tomography and the blood flow agent oxygen-15 water. Graded handgrip exercise, posthandgrip circulatory arrest, and administration of intra-arterial adenosine were performed to clarify the mechanisms controlling renal blood flow during static exercise. The major new findings in this study are that in healthy humans (1) renal cortical blood flow decreases (basal versus handgrip, 4.4 +/- 0.1 versus 3.5 +/- 0.1 mL [center dot] min sup -1 [center dot] g sup -1; P=.008) and renal cortical vascular resistance increases (basal versus handgrip, 17 +/- 1 versus 26 +/- 2 U; P=.01) in response to static handgrip exercise; (2) central command and/or the mechanoreflex contributes importantly to the early decrease in renal blood flow (basal versus handgrip, 4.2 +/- 0.2 versus 3.5 +/- 0.3 mL [centered dot] min sup -1 [center dot] g sup -1; P=.04) and to the increase in renal cortical vascular resistance (basal versus handgrip, 20 +/- 1 versus 25 +/- 2 U; P=.04); (3) the muscle metaboreflex contributes to further decreases in renal blood flow (basal versus posthandgrip circulatory arrest, 4.3 +/- 0.1 versus 3.5 +/- 0.2 mL [centered dot] min sup -1 [center dot] g sup -1; P=.002) and increases in renal cortical vascular resistance (basal versus handgrip, 18 +/- 1 versus 25 +/- 3 U; P=.002); and (4) exogenous adenosine activates the muscle metaboreflex producing reflex renal vasoconstriction and decreased renal blood flow, which may implicate endogenous adenosine generated during ischemic exercise as a potential activator of the muscle metaboreflex during ischemic handgrip exercise. (Circ Res. 1997;80:62-68.)