The effects of inosine on sinus rate and atrial contractile force were investigated using the isolated and blood-perfused canine atrium which was perfused with arterial blood from a donor dog. Injected inosine (100-3000 micrograms) consistently induced positive chronotropic and inotropic effects. However, the larger doses of inosine (1000 and 3000 micrograms) frequently produced slight and brief negative inotropic and chronotropic effects followed by long-lasting positive ones. Positive responses were not suppressed by treatment with propranolol. Negative responses were not inhibited by treatment with atropine. Adenosine-induced negative chronotropic and inotropic effects were potentiated by a continuous infusion of inosine at larger doses of 800-1000 micrograms/min. From these results, we concluded that inosine may have direct positive chronotropic and inotropic actions and that it potentiates adenosine-induced cardiac actions.