BACKGROUND The aim of this study was to identify specific characteristics associated with modifications of symptoms and to evaluate the presence of a pathophysiological link between radionuclide abnormalities and delayed run-off of coronary contrast dye in patients with angina and normal coronary arteries. METHODS We followed up 53 patients (21 men and 32 women, mean age: 52 +/- 10 years) with angina and angiographically normal epicardial coronary arteries, 21 of whom (40%) displayed a pattern of slow contrast dye run-off from coronary vessels, on visual assessment using a semiquantitative empirical score. Exercise tests showed ECG abnormalities in 29 patients (55%). RESULTS All patients were alive 92 +/- 44 months after catheterization (140 +/- 79 months after beginning of symptoms). However, 30 patients (57%), who reported worsening or no change of symptoms, presented with a non-significant higher prevalence of conduction abnormalities at rest ECG (27 versus 17%), pathological exercise tests (57 versus 52%), and delayed run-off (47 versus 30%). Regional left ventricular function and perfusion were then simultaneously assessed at rest and peak exercise with 99mTc-sestamibi. Exercise-induced radionuclide abnormalities were detected in 27 patients (51%), who also presented with a non-significant higher prevalence of pathological exercise tests (63 versus 43%) and no improvement of symptoms (63 versus 46%). However, exercise-induced functional and perfusional abnormalities were simultaneously present in 29 out of 42 (69%) coronary territories supplied by vessels with delayed run-off, versus 21 out of 117 (17%) normal territories (P = 0.00032). CONCLUSIONS Despite a good prognosis, some patients with angina and normal coronary arteries presented no improvement of symptoms at follow-up, and had functional and perfusional abnormalities in coronary territories supplied by vessels showing delayed contrast dye run-off.