Light and electron microscopic stereological studies were performed on the myocardium of spontaneously hypertensive rats (SHR-SP) before and after treatment with nifedipine (27 mg/kg body weight/day) and the antisympathotonic agent moxonidine (8 mg/kg body weight/day). The treated groups were compared with nontreated SHR-SP and normotensive WKY (n = 10 in each group). At the beginning of therapy (when the male SHR-SP were 6 months old), blood pressure was increased and left ventricular hypertrophy had developed whereas pathologic changes of myocardial structure were not observed. After 3 months, the nontreated hypertensive rats showed cardiac fibrosis, activation and proliferation of interstitial cells, wall thickening of intramyocardial arteries, reduced capillarization as well as focal degeneration of myocytes at the ultrastructural level. Both treatments showed similar effects on blood pressure, degree of hypertrophy, and cardiac structure. Blood pressure as well as the degree of hypertrophy were significantly reduced. As far as myocardial fibrosis, capillarization, and regressive changes of myocytes are concerned a complete normalization was observed. Furthermore, nifedipine enhanced capillary supply beyond the normal level by induction of capillary neoformation. Microarteriopathy and activation of nonvascular interstitial cells (first step in development of interstitial myocardial fibrosis) were significantly suppressed by therapy, but the level of the normotensive control could not be maintained. Additional experiments with a low dose combination therapy of nifedipine and moxonidine that did not reduce blood pressure provided evidence that hypertension is an important determinant of the alterations of intramyocardial arteries, but not of cardiac interstitial fibrosis.