The Ca2+-activated myosin ATPase activity in isoproterenol-induced hypertrophied left ventricle increased by 20-30% while in Goldblatt rats hypertrophy occurred with a decreased myosin ATPase activity. In non-dissociating (pyrophosphate) gel electrophoresis isoproterenol treatment showed decreased V2 and V3 myosin isozymes; at the higher dose of isoproterenol (0.5 mg/kg body weight) only V1 was present. In contrast a shift toward the V3 isozyme is present in the ventricles of Goldblatt rats. One group of rats was treated with toxic doses of digitoxin: no hypertrophy occurred but there was a disappearance of V1 and V2 isozymes and a 50% decrease in Ca2+-activated ATPase activity. Thus low doses of isoproterenol produce hypertrophy with an isozyme pattern similar to that found in young (approximately 4-6 weeks old) rats. The results with digitoxin show that shifts in the cardiac isozyme distribution can occur without hypertrophy.