The direct renal hemodynamic effect of two different vasodilators, diazoxide and acetylcholine, in the anesthetized dog, were studied. In 12 dogs (Group 1), diazoxide was given first directly into the renal artery and was followed by the addition of acetylcholine. In 6 dogs (Group 2) the order of drug administration was reversed. The glomerular filtration rate (GFR), the effective renal plasma flow (ERDF), and the excretion of sodium, potassium, chloride, and urine output were determined for both control and experimental (infused) kidneys. Both drugs when given alone resulted in a significant increase of all parameters tested on the experimental kidney, except the ERPF which was spuriously decreased by diazoxide. The addition of either drug upon the first given did not produce and further effect. It was, therefore, concluded that the hemodynamic changes, as well as the handling of electrolytes and water by the kidney, were solely due to the vasodilating properties of both compounds. A local renal tubular effect by diazoxide concerning sodium excretion could not be substantiated by our studies.