We compared exercise test results to a physiologic depiction of stenosis severity, coronary flow reserve (CFR), measured with a Doppler guide wire in 35 patients with single-vessel coronary disease. Group 1 (n = 21) had abnormal CFR, and group 2 (n = 14) had normal CFR. In group 1, 14 of 21 had ST-segment depression versus 3 of 14 in group 2 (p < 0.01). Exercise treadmill time (Bruce protocol) was normalized to the age- and sex-predicted time. Exercise time and normalized exercise time were less in group 1 (5.6 +/- 2.3 vs 9.9 +/- 1.8 min and 0.82 +/- 0.32 vs 1.25 +/- 0.23, p < 0.00001). Having either ST-segment depression or a normalized exercise time <1 during exercise had a 95% sensitivity, 71% specificity, and 86% predictive accuracy in identifying abnormal CFR. Coronary stenoses and minimal lumen diameter were similar in groups 1 and 2. By using stepwise logistical regression analysis, exercise time and ST-segment depression predicted CFR with a total r2 of 0.51. Minimal lumen diameter did not significantly add to the model. Exercise test variables, ST-segment depression, and exercise time are predictive of the physiologic significance of coronary lesions.