To assess the feasibility and the value of thallium-201 myocardial perfusion imaging with intravenous dipyridamole in combination with low-level exercise, 81 patients with suspected or proven coronary artery disease were studied. All patients underwent coronary arteriography. Significant coronary artery disease (stenoses greater than or equal to 50%) was present in 59 patients (73%); multivessel disease (double- and triple-vessel disease) was observed in 33 patients (42%). The overall sensitivity and specificity of the test were 78% and 86%, respectively. Sensitivity and specificity for detection of multivessel disease were 70% and 92%, respectively. The sensitivity for detecting coronary artery disease in the RCA, LAD, and LCX was 74%, 82% and 48%, respectively, and the specificity was 85%, 88% and 88%, respectively. With the combined procedure no serious side effects were observed. Mild side effects like headache, vertigo and nausea were seen in 12 patients (15%). Twenty volunteers with a less than or equal to 1% likelihood of significant coronary artery disease were examined in the same manner to determine the maximal specificity of the procedure (100%). Thus, the combination of two different stress procedures (exercise testing and dipyridamole infusion) can be performed safely without serious side effects. The presence, location and extent of significant coronary artery disease can be assessed to a similar degree as with conventional exercise thallium-201 scintigraphy, which has major implications for the detection of coronary artery disease in patients who are unable to perform maximal exercise.