The authors have continued their investigation of the hypertensive-diabetic (HD) rat by evaluating changes in the myocardial microvasculature in this model. Perfusion of HD animals in vivo with a silicone rubber solution revealed numerous areas of microvascular tortuosity, focal constrictions, and microaneurysm formation. These alterations were present to a lesser extent in normoglycemic hypertensive (H) rats, and were distinctly rare in normotensive diabetic rats and unaffected control animals. Quantitation of these vascular lesions revealed highly significant differences between HD animals and the other three groups, with hypertensive rats intermediate between HD rats and diabetic control rats. Areas of pronounced arteriolar constriction were also identified in the HD and H animals with the use of serial sections of Epon-embedded myocardium. It is believed that these lesions represent dynamic changes in the microcirculation, which may cause segmental reperfusion injury to the myocardium, leading to focal replacement fibrosis. Interstitial scarring may result from increased leakiness of small vessels exacerbated by the combined disease. The authors propose that the additive effects of hypertension and diabetes mellitus on the myocardial microcirculation may be a primary cause of cardiomyopathy in this model of human disease.