The hearts from C57BL/KsJ db+/db+ [genetically diabetic] mice and controls were examined by EM and [genetically obese] light microscopy at intervals during 5-28 wk of age. C57BL/6J ob/ob [genetically obese] and mice and their lean littermates served as other controls. The percentage of increase in body and heart weights of the diabetic animals was 150% and 64% greater, respectively, than that of the controls. Over the period of observation, there was progressive damage to the ventricular myocytes and intramural small arteries and arterioles of the diabetic animals. Initially, the cardiac muscle cells of both ventricles contained large numbers of lipid droplets. Shrinkage and increased electron density of mitochondria enveloped by single limiting membranes then gave rise to large residual bodies, followed by loss of myofilaments and atrophy of myocytes. Similar changes occurred in the smooth muscle cells of intramural arteries and arterioles but not in those of epicardial arteries. Reduplicated layers of basal laminae were seen around interstitial capillaries. Degenerative changes which occurred in perivascular nerve endings are discussed in relation to the altered metabolism of the diabetic state. The pathologic lesions in cardiac muscle cells and intramural arterial vessels and capillaries constitute a primary myocardial disease in the genetically diabetic mouse.