The hemodynamic effect of insulin was examined in isolated perfused kidneys. Experiments were designed to study the effect of the hormone on basal hemodynamics and in the presence of angiotensin II (ANG II). Physiological insulin concentrations caused both renal vasodilation and increased glomerular filtration rate (GFR) during basal perfusion periods and attenuated the vasoconstrictor action of ANG II while limiting the ANG II-induced reduction of GFR. Insulin also increased fractional sodium reabsorption and diminished the natriuretic effect of ANG II. The addition of insulin to perfusions in which ANG II was infused from the start caused renal vasodilation, although supraphysiological concentrations were required. Kidneys perfused with hyperoncotic albumin to prevent filtration similarly demonstrated a vasodilatory effect of insulin that did not require glomerular filtration. Inhibition of prostaglandin (PG) synthesis with indomethacin prevented the vasodilatory effects of insulin. These data support the hypothesis that insulin causes renal vasodilation by a PG-dependent process.