The cardiotoxic effects of Adriamycin (ADM) were studied utilizing mammalian myocardial cells in culture as a model system. ADM inhibited cell growth and the rhythmic contractions characteristic of these cells. Because a possible involvement of energy metabolism in the action of ADM was suggested previously, the adenylate energy charge and phosphorylcreatine mol fraction were determined in the ADM-treated cells. The adenylate energy charge was found to be significantly decreased, while the phosphorylcreatine mol fraction was not. Such disparity suggests an inhibition of creatine phosphokinase. The addition of 1 mM adenosine to the myocardial cell cultures markedly increased the adenosine triphosphate concentration but not the adenylate charge. In the ADM-treated cells, the addition of adenosine increased both the adenosine triphosphate concentration and the adenylate charge, and, concomitant with this increase, the functional integrity of the cells in terms of percentage of beating cells and rate of contractions was maintained.