Variance electrocardiography (variance ECG) is a new resting procedure for detection of coronary artery disease (CAD). The method measures variability in the electrical expression of the depolarization phase induced by this disease. The time-domain analysis is performed on 220 cardiac cycles using high-fidelity ECG signals from 24 leads, and the phase-locked temporal electrical heterogeneity is expressed as a nondimensional CAD index (CAD-I) with the values of 0-150. This study compares the diagnostic efficiency of variance ECG and exercise stress test in a high prevalence population. A total of 199 symptomatic patients evaluated with coronary angiography was subjected to variance ECG and exercise test on a bicycle ergometer as a continuous ramp. The discriminant accuracy of the two methods was assessed employing the receiver operating characteristic curves constructed by successive consideration of several CAD-I cutpoint values and various threshold criteria based on ST-segment depression exclusively or in combination with exertional chest pain. Of these patients, 175 with CAD (> or = 50% luminal stenosis in 1 + major epicardial arteries) presented a mean CAD-I of 88 +/- 22, compared with 70 +/- 21 in 24 nonaffected patients (p < 0.01). Variance ECG provided a stochastically significant discrimination (p < 0.01) which was matched by exercise test only when chest pain variable was added to ST-segment depression as a discriminating criterion. Even then, the exercise test diagnosed single-vessel disease with a significantly lower sensitivity. At a cutpoint of CAD-I > or = 70, compared with ST-segment depression > or = 1 mm combined with exertional chest pain, the overall sensitivity of variance ECG was significantly higher (p < 0.01) than that of exercise test (79 vs. 48%). When combined, the two methods identified 93% of coronary angiography positive cases. Variance ECG is an efficient diagnostic method which compares favorably with exercise test for detection of CAD in high prevalence population.