The effect of intracoronary papaverine administration on epicardial coronary arterial diameter was examined in 18 male patients. Coronary-artery cineangiograms were acquired with a power injector before intervention, 20 sec after intracoronary saline (control), and 20 sec after administration of papaverine into either the left (12 mg) or right (8 mg) coronary artery. Absolute coronary arterial diameter of a normal-appearing segment was quantified using a previously validated, fully automated digital edge detection program with an ADAC digital radiographic unit. Baseline coronary arterial diameter of 3.1 +/- 0.8 mm did not significantly change after saline administration (3.1 +/- 0.9 mm) but did significantly increase (p less than .001) to 3.4 +/- 0.9 mm after papaverine administration. No significant percent change in diameter occurred in either the left anterior descending (-.5 +/- 1.7%), left circumflex (-.2 +/- 1.1%), or right (-3.0 +/- 3.8%) coronary arteries with saline, but significant (p less than .001) increases occurred with papaverine (7.2 +/- 4.1%, 7.0 +/- 4.5%, 6.8 +/- 2.7%, respectively). The response of 7 coronary arteries examined immediately proximal to a significant lesion was not significantly different from the response of the remaining 11 coronary arteries. In conclusion, intracoronary papaverine causes a significant increase in coronary arterial diameter. This has clinical implications for assessing coronary flow reserve with devices that defect flow velocity.