Histamine is widely present in human tissues and can be released by immunologic and nonimmunologic reactions. Although several direct cardiovascular effects of histamine have been demonstrated in humans, little is known about the direct effects of histamine on the human coronary circulation in vivo. Therefore, we investigated the changes in coronary hemodynamics induced by bolus intracoronary administration of 4 micrograms of histamine to 11 patients with angiographically normal coronary arteries under continuous monitoring of R-R interval from the electrocardiogram, arterial pressure (AP), and coronary sinus blood flow (CBF), measured by thermodilution. Immediately after the end of the intracoronary histamine bolus, with R-R interval and AP unchanged, CBF increased from 144 +/- 20 to 238 +/- 27 ml/min (p less than 0.01) and coronary vascular resistance decreased from 0.7 +/- 0.16 to 0.42 +/- 0.1 mm Hg/ml/min (p less than 0.01). No change in coronary hemodynamics was observed after bolus intracoronary administration of physiologic saline. The effects of histamine on systemic hemodynamics consisted of a transient fall in AP and R-R interval, starting after the onset of changes in coronary hemodynamics. These data show that histamine possesses a direct coronary vasodilator effect in humans, independent of the determinants of myocardial oxygen consumption.