Effects of hypertonic urea solution on potassium contracture were investigated in a bullfrot ventricular strip. In a medium of three times hypertonic urea, the contracture induced by 100 mM potassium solution was markedly inhibited whereas the twitch contraction was augmented in the hypertonic urea solution. The extent, as well as the time course, of the membrane depolarization produced by high potassium solution was essentially identical in both isotonic and hypertonic conditions. Endogeneous catecholamine does not seem to participate in this inhibition since the treatment with propranolol did not modify the results. Thus, the possibility of the well-known catecholamine-induced inhibition of potassium contracture can be excluded. The myocardial contractility was never suppressed, or even augmented, at this stage of urea perfusion although a prolonged hypertonic urea perfusion gradually suppressed the contractility. It was suggested that hypertonic urea exerts its negative inotropic action on the potassium contracture independently of its positive inotropism on the twitch contraction by accelerating the uptake of the activator calcium ion to some undefined intracellular sites.