Cardiac myosin was examined during the 4 pathologic stages of cardiomyopathy in strain BIO 14.6 of Syrian hamsters. The Ca2+- and K+-EDTA activated ATPase activities of ventricular myosin were significantly reduced during the final stage of the inherited disease. The 1- and 2-dimensional gel electrophoreses of myosin samples at all stages failed to yield any evidence for a change in the subunit structure of myosin based on L chain number, MW and per cent composition. The final stage of the disease was characterized by altered protein metabolism. The rates of synthesis and degradation were altered in the diseased tissue, with a net loss of myosin resulting from a substantial increase in the rate of degradation.