A decrease in cardiac function and intracellular calcium, and an increase in cardiac sarcolemmal ATPase have been reported in experimentally induced aortic stenosis of 6 to 9 months duration. Prazosin has been used in the treatment of heart failure due to mechanical ventricular overload. It is, however, not known whether prazosin treatment gives only hemodynamic benefit with accompanying subjective improvement or if it also improves the condition of the myocardium in terms of contractility and biochemical changes. The present investigation deals with the effects of 3 months of prazosin treatment on cardiac function, electrolytes, and ATPase in dogs with aortic stenosis of 3 months duration. Although there were no significant changes in most of the left and right ventricular hemodynamic parameters, the left ventricular enddiastolic pressure increased significantly after 3 months of aortic stenosis. Prazosin prevented further deterioration of cardiac function. All the dogs developed left ventricular hypertrophy and all chest X-rays showed cardiomegaly. Concomitant with these changes, there was a tendency towards a decrease in total tissue Ca⁺⁺ and intracellular Ca⁺⁺ and K⁺ and a tendency towards an increase in sarcolemmal Na⁺-K⁺-ATPase. Prazosin treatment, although it markedly reduced left ventricular end-diastolic pressure, did not reduce the cardiomegaly. There were no significant changes in any of the other hemodynamic parameters. Prazosin treatment decreased sarcolemmal ATPase and tended to increase intracellular Ca⁺⁺. It appears therefore that prazosin not only tends to bring the cardiac function towards control values but also tends to correct the ATPase and intracellular Ca⁺⁺ levels of the failing heart.