Adenosine may mediate coronary vasodilation during work-related hyperemia and during ischemia. We tested whether adenosine blockade with 8-p-sulfophenyltheophylline (PSPT) prevented dobutamine-induced hyperemia or magnified the reductions in flow due to vasopressin. Control (n = 8) and test (n = 7) dogs received paired infusions of dobutamine (70 micrograms/min iv for 5 min). Test dogs received PSPT (10 mg/kg iv) between doses. In both groups, paired infusions elicited comparable increases in oxygen consumption. However, in test dogs, the hyperemia was reduced significantly. Thus adenosine mediates the hyperemia of dobutamine. Separately, control dogs (n = 9) received vasopressin (0.6 microgram ic over 5 min); test dogs (n = 7) received PSPT before vasopressin. Vasopressin maximally increased coronary resistance by 3 min; effects were gone by 10 min. With PSPT, coronary resistance was increased further and remained high beyond 10 min. Thus adenosine-mediated vasodilation moderates the severity and duration of ischemia. These results indicate the importance of adenosine in mediating coronary flow during increased demand and reduced supply.