To compare the accuracy of supine bicycle stress echocardiography (SBSE), a new technique for evaluating coronary disease during peak exercise, with tomographic thallium-201 exercise imaging (SPECT), 71 patients were evaluated by SBSE, SPECT, and coronary arteriography. Twenty patients had normal coronary vessels; 22 had single-vessel, 14 had double-vessel, and 15 had triple-vessel disease. There were no differences in sensitivity (90% vs 92%), specificity (80% vs 65%), and accuracy (87% vs 85%) between SBSE and SPECT for the group of 71 patients. The results were similar in patients with and without prior myocardial infarction and with single-, double-, or triple-vessel disease. There were no differences between SBSE and SPECT for disease detection for the group of 213 individual vessels in sensitivity (88% vs 80%), specificity (87% vs 84%), and accuracy (88% vs 82%), but SBSE was more sensitive for the left anterior descending artery (97% vs 82%, p < 0.005) and for arteries involved in triple-vessel disease (93% vs 69%, p < 0.01) and more specific for the right coronary artery (88% vs 66%, p < 0.01). Supine bicycle exercise was associated with significantly lower maximal heart rates than treadmill exercise but with significantly higher systolic and diastolic blood pressures. There were no differences in heart rate x systolic blood pressure. We conclude that SBSE and SPECT are equally reliable for coronary disease detection in patients and for evaluation of disease in specific arteries with the exception of SBSE's higher sensitivity for the left anterior descending artery and arteries involved in triple-vessel disease and higher specificity for the right coronary artery.