To determine whether hemodynamic changes can modulate insulin action in vivo, we administered angiotensin II (A,,) to normal men under three separate, euglycemic conditions. First, in the presence of physiological hyperinsulinemia (-115 5,U/ml), infusion of A,, at rates of 2, 10, and 20 ng/min per kg caused significant elevations of blood pressure, whole-body glucose clearance, and plasma insulin concentrations in an Al, dose-dependent manner. Second, in the presence of plasma insulin concentrations that stimulate glucose transport maximally (-5,000 ,U/ml), A,, infusions increased whole-body glucose clearance without enhancing glucose extraction across the leg.Third, in the presence of basal insulin concentrations (.13 igU/ml), A,, infusions had no effect on whole-body glucose turnover or leg glucose extraction. Thus, A,, enhanced whole-body glucose utilization without directly stimulating glucose transport in a major skeletal muscle bed. To evaluate a possible hemodynamic mechanism for the effects of A,, on glucose utilization, we measured blood flow to two areas that differ in their sensitivity to insulin: the kidneys and the leg. We found that A,, redistributed blood flow away from the predominantly insulinindependent tissues of the kidney and toward the insulin-sensitive tissues of the leg during both sham and hyperinsulinemic glucose clamps. The redistribution of flow had no effect on whole-body glucose turnover when leg glucose uptake was unstimulated (sham clamps). However, when leg glucose uptake was activated by insulin, the redistribution of flow caused a net increase in whole-body glucose utilization. Our findings indicate that hemodynamic factors can modulate insulin action in vivo. Furthermore, our results suggest that variable activity of the renin-angiotensin system may contribute to inconsistencies in the association between insulin resistance and hypertension.