The potent converting enzyme inhibitor (CEI) SQ14,225, which is known to prevent the formation of angiotensin II (AII) has been used to evaluate the role of AII in the development and reversal of cardiac hypertrophy. The present study describes the effect of CEI on blood pressure (BP) and myocardial hypertrophy (prevention and reversal) in the spontaneously hypertensive rat (SHR). A group of 3-week- and 8-week-old male SHR was treated with CEI (30 mg/kg in drinking water) for 6 weeks. An additional group of SHR was also treated with a combination of CEI and a diuretic (hydrochlorothiazide, 500 mg/liter). Heart weight, BP, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), hydroxyproline, myocardial catecholamines, and plasma renin activity (PRA) were determined. In the prevention study, we found a significant reduction in the ratio of heart weight to body weight along with the prevention of hypertension (200 vs 145 mm Hg, p less than 0.001). Similar reductions in BP and heart weights were obtained with the reversal group. A better BP control was noted in the CEI and hydrochlorothiazide group. The reduction of heart weight was associated with a reduction in RNA and hydroxyproline content. In all groups, we found a significant increase in PRA (p less than 0.001) and a slight increase in tissue catecholamine concentration. No change in kidney weight was found in any group. Data clearly showed that oral administration of CEI prevented and reversed cardiac hypertrophy in SHR. Reversal was associated with a decrease in myocardial collagen content. These data indicate that prevention of AII formation in combination with BP control can prevent and reverse cardiac hypertrophy in SHR. Of course, whether or not CEI acts only through the renin angiotension system is still speculative.