The mechanism by which the administration of large doses of catecholamines produces myocardial necrosis in experimental animals and humans has not yet been ascertained. One of the consequences of such administration is the accumulation of high concentrations of Ca in the heart and it has therefore been suggested that this is the factor that leads to cell injury. The elevated intracellular Ca appears to be due in part to enhanced Ca influx resulting from catecholamine-induced opening of membrane Ca channels and in part to increased membrane permeability caused by membrane damage. It is not clear, however, why the myocardial cells are unable to extrude their extra load of Ca, at least initially, so as to maintain normal Ca concentrations. The effects of high concentrations of epinephrine and isoproterenol on Na+-Ca2+ exchange transport in isolated sarcolemmal vesicles prepared from hearts of Sprague-Dawley rats were determined. It was found that catecholamine concentrations of 10(-4) to 10(-2) M inhibited the exchange in a dose-related manner while choline, in the same concentrations, had no effect. It is therefore possible that cardiotoxic concentrations of catecholamines also interfere with Na+-Ca2+ exchange transport across the myocardial sarcolemma in vivo and thereby inhibit the efflux of intracellular Ca.