The effects of dipyridamole and adenosine on the renal vasculature and on the enhancement by dipyridamole of the action of adenosine were studied in pigs, dogs, rabbits, and rats. Intravenous adenosine in doses of 10-300 micrograms/kg produced dose-dependent decreases in heart rate and blood pressure of rabbits and rats. Potentiation of adenosine action by intravenous infusion of dipyridamole occurred only in rabbits. When administered into the renal artery of pigs, dogs, rabbits, and rats, adenosine caused dose-dependent vasoconstriction in all species, whereas dipyridamole produced vasoconstriction in rabbits and vasodilation in pigs and rats. In dogs, the renal vascular response to dipyridamole depended on the perfusion method used. In kidneys perfused at a fixed flow rate with a pump, intrarenal dipyridamole elicited vasoconstriction, but in kidneys perfused by their own systemic blood pressure without the use of a pump, it caused vasodilation. The adenosine-induced renal vasoconstriction was enhanced by dipyridamole in pigs, dogs, and rabbits, but not in rats. Species differences and the perfusion method used are important for the renal vascular effects of dipyridamole. Dipyridamole appears to possess not only an indirect action on blood vessels which is related to adenosine, but also a direct vasodilator effect.