The relative sensitivity and specificity of individual and combined noninvasive tests to detect coronary heart disease were evaluated in 75 patients with chest pain admitted for cardiac catheterization and coronary arteriography. Of the 75 patients, 56 had coronary heart disease. Exercise-induced ST-segment abnormalities (≥1 mm) were found in 58%. In contrast, computer-processed exercise thallium-201 perfusion imaging detected 82% (p<0.01) and assessment of regional ejection fraction at rest and during isometric exercise by radionuclide angiography detected 82% (p<0.02). Pathologic Q waves were present in 20%. Of nine patients with single-vessel disease, only one had exercise ST-segment abnormalities, while four had abnormalities in thallium-201 perfusion and five in regional ejection fraction. Of 16 patients with two-vessel disease, 10 had ST-segment abnormalities, 14 had defects on thallium-201 imaging and 13 had abnormalities in regional ejection fraction. Similary, of 31 patients with three-vessel coronary heart disease, 23 had exercise-induced ST-segment changes, while 28 had thallium-201 perfusion defects and 28 had abnormalities in regional ejection fraction. Combined noninvasive testing using pathologic Q waves and exercise ST-segment abnormalities detected 71% of patients with coronary heart disease. Addition of exercise thallium-201 imaging resulted in 88% of patients being detected, and addition of regional ejection fraction detected 96%. If an abnormality in any of the four tests was considered, 55 of 56 patients (98%) with coronary heart disease were detected. In 19 patients with normal coronary arteries, the specificity of the exercise ECG was 84%, exercise thallium-201 imaging 89% and assessment of regional ejection fraction 79%. However, if all noninvasive tests were considered, the specificity decreased to 58%. Thus, either exercise thallium-201 imaging or assessment of regional ejection fraction is superior to exercise-induced ST-segment abnormalities. Combined testing results in a very high sensitivity, but there is a concomitant reduction in specificity.