Insulin sensitivity in essential hypertension and atherosclerosis has elicited substantial research interest. Hyperinsulinemia in prospective studies identifies patients at risk for the development of coronary atherosclerosis. Plasma renin activity has also been shown to predict myocardial infarction, and correlates inversely with insulin sensitivity in hypertensive patients. The current study investigated the relationship between plasma renin activity and insulin sensitivity in 25 normotensive subjects. Using the euglycemic clamp technique, the data show a significant inverse correlation between supine plasma renin activity and insulin-mediated glucose uptake (r = -0.44; P = .027). Significant relationships were also found between plasma renin activity and fasting insulin concentration and fasting serum triglycerides. Reductions in relative skeletal muscle blood flow during insulin infusion have been reported in insulin-resistant compared to insulin-sensitive subjects. Skeletal muscle is the main site of insulin action during euglycemic clamp study and angiotensin II increases skeletal muscle blood flow. Increasing plasma renin activity may reflect a metabolic compensation which offsets the relative reduction in insulin-mediated enhancement in skeletal muscle blood flow in insulin resistance by generation of angiotensin II, which in turn promotes skeletal muscle blood flow.