Calcium antagonists are used in interventional cardiology to prevent coronary vasoconstriction or to overcome the no-reflow phenomenon. The aim of the current study was to evaluate the dose-dependent effects of intracoronary verapamil on systemic and coronary hemodynamics. In 20 patients scheduled for routine coronary angiography, heart rate, blood pressure, and ECG recordings were recorded continuously and intracoronary flow velocity was obtained by intracoronary Doppler measurements in angiographically normal vessels. The cross-sectional area, measured by quantitative coronary angiography, allowed the calculation of coronary blood flow (CBF) and the coronary vascular resistance index (CVRI). Without premedication, increasing dosages of verapamil (0.01 mg, 0.1 mg, 1.0 mg, and 2.0 mg) were injected into the left coronary artery. Intracoronary verapamil administration led to a decrease in systemic blood pressure only after administration of 1.0 mg or 2.0 mg (change in mean arterial pressure: from 87.6 +/-14.6 mmHg to 80.1 +/- 14.9 mmHg and 78.5 +/- 13.9 mmHg, respectively; both P < 0.05) without a change in heart rate. Epicardial diameters of the left coronary artery increased only at dosages of 1.0 mg and 2.0 mg (from 2.14 +/- 0.4 mm to 2.22 +/- 0.3 mm, P < 0.01), whereas the coronary blood flow velocity increased significantly at the smallest dosage of 0.01 mg (from 19.9 +/- 8.7 cm/s to 33.2 +/- 14.9 cm/s, P < 0.001) and was further enhanced with increasing dosages. CBF increased and CVRI decreased at every dosage of verapamil compared with baseline values. CBF increased also after 0.1 mg (from 13.5 +/- 6.5 mL/min to 19.5 +/- 9.3 mL/min; P < 0.05), reaching a maximal effect after administration of 1.0 mg verapamil (26.3 +/- 16.1 mL/min, P < 0.05). Application of 2.0 mg did not further increase CBF compared with 1.0 mg. Intracoronary application of verapamil leads to a decrease in systemic blood pressure at higher dosages, whereas heart rate remains unchanged at any dosage. The maximal increase in coronary blood flow and decrease in vascular resistance can be reached by administration of 1.0 mg verapamil into the left coronary artery.