The hamster hereditary cardiomyopathy provides a unique model for the study of membrane abnormalities during chronic congestive heart failure. It is associated with intracellular calcium accumulation, mitochondrial calcification and cell necrosis. Previous studies have shown a decrease in Na, K-ATPase activity purified from ventricle sarcolemma. The present study demonstrates a decrease in K-dependent 3-O-methylfluorescein phosphatase (3-O-MFPase) activity from 1.93 to 1.30 μmol/g wet wt. or 33% in crude homogenates from the left ventricle of 7-months-old cardiomyopathic hamsters as compared to control animals. This represents an equivalent decrease in Na, K-ATPase activity. The values are several times higher than previously published for membrane fractions of myocardium from the hamster. Concomitantly, there was an increase in intracellular Na-concentration of the myocardium of 42% whereas the K-concentration was unchanged. The decrease in Na, K-pump concentration may be of importance for the increase in intracellular sodium and ensuing calcifying necrosis observed in the myocardium of cardiomyopathic hamsters. It is emphasized that quantification of the Na, K-ATPase or Na, K-pump should preferably be performed using crude homogenates.