To compare the relative diagnostic value of exercise echocardiography with perfusion technetium-99m metoxyisobutylisonitrile single-photon emission computed tomography (SPECT) in detecting coronary artery disease (CAD), 75 patients with suspected CAD but a normal electrocardiogram (ECG) at rest were included in a prospective correlative study. Both the exercise echocardiograms and SPECT studies were performed in conjunction with the same symptom-limited bicycle exercise test. The development of either a new wall motion abnormality or a reversible perfusion defect after exercise, or both, were regarded as a positive test for the exercise echocardiographic and SPECT studies, respectively. The results of these 2 diagnostic tests were compared with coronary arteriography. Exercise echocardiography identified 35 (71%) and SPECT 41 (84%, p = 0.13) of the 49 patients with significant CAD (defined as greater than 50% diameter stenosis). Twenty-five of the 26 patients (96%) without significant coronary stenosis had negative exercise echocardiographic results and 23 of 26 (88%) had negative SPECT results. Exercise-induced new wall motion abnormalities showed a good correlation with reversible perfusion defects, and the results of the 2 methods were concordant in 65 of 75 patients (agreement = 88%, kappa = 0.75 +/- 0.14). Both the diagnostic accuracy of exercise echocardiography and SPECT were significantly higher than the exercise ECG (81 vs 64%, p less than 0.02 and 88 vs 64%, p less than 0.005). The sensitivity and specificity for detecting individual diseased vessels were 60 and 95% for exercise echocardiography and 67 and 94% for SPECT.(ABSTRACT TRUNCATED AT 250 WORDS)