The significance of a decline in systolic blood pressure (BP) during supine exercise was examined in 820 patients who underwent both supine exercise gated equilibrium radionuclide ventriculography and coronary angiography. Twenty-seven patients, 3% of the study population, had a decrease in systolic BP at peak exercise of more than 10 mm Hg from the systolic BP at rest. Other indicators of ischemia--angina, ST-segment depression, a decrease in ejection fraction and wall motion abnormality during exercise--were present frequently but not uniformly in these patients. Although most patients had a decline in ejection fraction and a new wall motion abnormality with exercise, 4 patients had an increase in ejection fraction with exercise without any regional wall motion abnormalities. Coronary angiography in the 27 patients with systolic hypotension demonstrated severe coronary artery disease (CAD). Twenty-two patients (81%) had 3-vessel or left main CAD. Twenty of these 22 patients with 3-vessel CAD had at least 2 arteries with 90% or more diameter stenoses. Systolic hypotension during supine exercise radionuclide angiography is infrequent, usually associated with evidence of global and regional left ventricular dysfunction, and a marker of very severe CAD.