It is now known that insulin has marked acute effects on plasma noradrenaline and the cardiovascular system. These effects of insulin are not due to hypoglycemia and occur without changes in plasma adrenaline. Intravenous injection of insulin in juvenile diabetics increased plasma noradrenaline and heart rate and decreased glomerular filtration rate, renal and peripheral blood flow, and plasma volume. Urinary excretion rates of beta-2-microglobulin and urinary volume decreased after insulin, whereas urinary albumin excretion increased. When blood glucose was maintained by glucose infusion after insulin, glomerular filtration rate and renal blood flow remained unaltered whereas plasma noradrenaline, heart rate, and urinary albumin excretion increased and beta-2-microglobulin excretion decreased. Decreases in glomerular filtration rate and renal blood flow after insulin are thus due to the fall in blood glucose. Rise in albumin excretion after insulin is probably of glomerular origin and not caused by the fall in blood glucose or by changes in renal hemodynamics. In patients with long-term diabetic nephropathy and albuminuria, insulin decreased albumin excretion (probably due to renal vasoconstriction) and plasma noradrenaline did not increase. In alloxan-diabetic rabbits the increase in heart rate after insulin was not abolished by autonomic blockade. In short-term streptozotocin-diabetic rats, muscle capillary endothelial cells showed a reduced number of free micropinocytotic vesicles. The number was nearly normalized 1 hr after intramuscular injection of insulin. The mechanism of action of insulin on plasma noradrenaline, heart rate, plasma volume, and urinary albumin excretion is not known. The rise in plasma noradrenaline after insulin may be compensatory to hypovolemia or to antagonizing effects of insulin on some actions of noradrenaline. The findings in streptozotocin-diabetic rats suggest that insulin may be essential for the normal function of capillary endothelial cells.