To date, no clinical study shows an improvement in coronary flow reserve due to long-term antihypertensive therapy. In view of the contribution of the renin-angiotensin system to the process of hypertensive remodeling of the heart and coronary circulation, angiotensin-converting enzyme (ACE) inhibitors might act as cardioreparative drugs in arterial hypertension. Accordingly, our objective in this investigation was to examine under clinical conditions to what extent long-term antihypertensive treatment with an angiotensin-converting enzyme inhibitor improved the diminished coronary flow reserve in hypertensive patients with microvascular angina pectoris. For the purpose of comparison, we also treated a normotensive control group of 6 patients with hypertrophic nonobstructive cardiomyopathy. Fifteen hypertensive individuals (10 men, 5 women; age, 58 plus/minus 6 years) were treated with enalapril (10 to 20 mg/d; mean, 16.7 plus/minus 4.9 mg/d) for 11 to 13 months. At the end of the treatment period, systolic pressure decreased from 178 plus/minus 14 to 137 plus/minus 12 mm Hg and diastolic pressure from 102 plus/minus 11 to 86 plus/minus 4 mm Hg under ambulatory conditions. Left ventricular muscle mass index decreased by 8%, from 149 plus/minus 32 to 137 plus/minus 28 g/m2(P < .05). Maximal coronary blood flow after dipyridamole was increased by 43%, from 181 plus/minus 69 to 258 plus/minus 116 mL/min per 100 g (P < .001), and minimal coronary vascular resistance was diminished by 29%, from 0.66 plus/minus 0.23 to 0.47 plus/minus 0.24 mm Hg [centered dot] min [centered dot] 100 g [centered dot] mL-1(P < .001) after enalapril treatment. Consequently, the calculated coronary reserve increased from 2.2 plus/minus 0.6 to 3.3 plus/minus 1.2 (P < .001). After enalapril therapy, the functional class of angina pectoris according to the Canadian classification system had changed from 2.5 plus/minus 0.6 to 1.5 plus/minus 0.6 (P < .01). The maximal working capacity had increased from 23.775 plus/minus 3.970 to 26.255 plus/minus 4.598 J (mean plus/minus SE, P < .05). The maximal ST-segment depression at maximal workload was reduced from 0.18 plus/minus 0.02 to 0.06 plus/minus 0.02 mV (mean plus/minus SE, P < .01). In summary, long-term therapy with the angiotensin-converting enzyme inhibitor enalapril must be considered a cardioreparative treatment with respect to the coronary microcirculation in hypertensive heart disease. (Hypertension. 1996;27:1031-1038.)