Upright and supine multiple gated cardiac blood pool scintigraphy was performed at rest and during maximum exercise in 37 patients, 15 with normal coronary arteriograms, 12 with coronary artery disease (CAD) without myocardial infarction (MI), and 10 with CAD and previous MI. Heart rate and systolic blood pressure were similar during upright and supine exercise in normal patients, but were significantly lower during supine exercise in both CAD groups. Left ventricular (LV) ejection fraction (EF), right ventricular (RV) EF, and LV segmental wall motion were similar in the upright and supine positions at rest or during maximum exercise within each group and showed high concordance of exercise responses. Although LV end-diastolic volume increased in all three groups during upright exercise and in both CAD groups when exercised supine, it did not change during supine exercise in patients without CAD. The fall of LV end-systolic volume in normals was greater during supine exercise than during upright exercise. LV end-systolic volume rose in the CAD patients in both positions. Therefore, although LVEF, RVEF, and LV segmental wall motion responses are similar in the upright and supine positions, LV end-systolic and LV end-diastolic volume changes are not. For detecting and evaluating CAD, the two different positions of exercise appear to have similar diagnostic content.