Background Adenosine 5'-triphosphate (ATP) has been demonstrated to have similar vasodilator potency and fewer hemodynamic or electrocardiographic derangements compared with papaverine in the measurement of coronary flow reserve. However, there is little data about its optimal dose and the effect on myocardial lactate metabolism. Methods Under continuous monitoring of the left anterior descending coronary flow velocity with a Doppler guide wire, we investigated the changes of hemodynamics, electrocardiogram, and myocardial lactate metabolism before and after the administration of 50 μg ATP and 10 mg papaverine into the left coronary artery in 18 patients with normal coronary arteries. To determine the optimal dose of ATP for the coronary flow reserve in the left coronary artery, we measured coronary flow velocity with five incremental doses of intracoronary ATP (0.5, 5, 15, 30, and 50 μg) and 10 mg of papaverine in another seven patients. Results In contrast to papaverine, ATP did not produce any significant changes in hemodynamics or the electrocardiogram. The increase in the coronary flow velocity of the two agents was similar. Although all patients showed lactate production after the administration of papaverine, only three patients showed lactate production after ATP (p < 0.001). The coronary flow reserve derived from ≥15 μg of ATP was similar to that derived from papaverine. There was a significant correlation between the coronary flow reserve obtained with ≥5 μg of ATP and that obtained with papaverine. Conclusions These results suggest that maximal coronary vasodilation in the left coronary artery can be safely obtained with doses ≥15 μg of intracoronary ATP in patients with normal coronary arteries. (Am Heart J 1998;135:621-7.)