Diabetic cardiopathy represents a cardiac disorder with involvement of myocardial, interstitial, coronary, and neural structures. One of the main manifestations refers to coronary microangiopathy, which has not yet been clearly identified. Coronary hemodynamics, including the determination of coronary flow reserve, were therefore analyzed in normal subjects and in nine patients with NIDDM and clinically suspected coronary heart disease but normal coronary arteriogram. Coronary flow reserve was determined as the quotient of baseline and minimal coronary resistance after dipyridamole (0.5 mg/kg i.v.). Coronary blood flow was measured quantitatively by the argon method. Systolic left ventricular function was analyzed by ventriculography and diastolic function by M-mode and Doppler echocardiography. Twelve healthy normotensive subjects served as the control group (CON). In the diabetic patients, maximal coronary flow was significantly reduced (172 ± 50 vs. 395 ± 103 ml/min × 100 g; P < 0.001), and minimal coronary resistance was increased (0.60 ± 0.19 vs. 0.24 ± 0.06 mmHg × min × 100 g/ml; P < 0.001). Coronary reserve in the diabetic subjects was markedly reduced (1.84 ± 0.39 vs. 4.23 ± 0.52; P < 0.001). No difference existed with respect to myocardial oxygen consumption (12.4 ± 2.3 vs. 11.8 ± 2.8 ml 0₂/100 g × min; NS). Global systolic function was normal in all patients (ejection fraction: NIDDM 72 ± 13 vs. CON 77 ± 12%, NS; CI: NIDDM 3.2 ± 0.8 vs. CON 3.3 ± 1.2 1/min × m², NS). Diastolic function was impaired in diabetic patients with an increase in relaxation time index (97 ± 23 vs. 45 ± 18 ms; P < 0.01) and an impaired diastolic inflow pattern, indicated by the ratio between early and late transmitrai flow (0.75 ± 0.14 vs. 1.66 ± 0.13; P < 0.05). We conclude that the markedly reduced coronary flow reserve in diabetic patients may play a key role in the induction and perpetuation of coronary insufficiency in myocardial ischemia, in diastolic and systolic dysfunction, and in the initiation of diabetic cardiopathy.