The sensitivity of myocardial perfusion imaging (MPI) using thallium-201 injected both at rest and during peak exercise was compared to simultaneously recorded 12 lead electrocardiography (ECG) for the detection of transient ischemia in 20 normal subjects and 63 patients with coronary artery disease (CAD). No significant perfusion defects or ECG changes were seen on either the rest or exercise studies in any of the normal subjects. Fifty-six percent of patients with CAD developed new perfusion defects with exercise compared to 38% who developed ischemic ST-segment depression (P less than 0.02). However, when chest pain and/or ST depression were considered indices of ischemia, the sensitivity of exercise testing and thallium-201 MPI was similar. The increased sensitivity of MPI compared to ST-segment depression on the ECG was due to patients with baseline ECG abnormalities and those who failed to achieve 85% of predicted maximum heart rate with exercise. Analysis of the exercise results according to the extent of coronary artery disease revealed a progressive increase in both positive ECGs and MPI with the number of vessels involved. In patients with single vessel disease the MPI was more sensitive than the ECG (P less than 0.02). The combination of the rest and exercise ECG, MPI and chest pain during exercise failed to identify 11% of patients with CAD. Exercise thallium-201 MPI is a useful adjunct to conventional exercise testing particularly when evaluating patients with abnormal resting ECGs, those who develop ventricular conduction defects of arrhythmias during exercise, and those who fail to achieve their predicted heart rate because of fatigue or breathlessness.