This study tests the hypothesis that myocardial ischemia is responsible for exercise-induced S-T segment elevation in patients with previous anterior myocardial infarction (MI). Exercise stress testing in conjunction with thallium imaging of the myocardium was performed in 28 patients with previously documented anterior MI. Thallium images were analyzed by computer for the presence of initial uptake defects and evidence of abnormal clearance of the isotope from the myocardium (that is, imaging evidence of ischemia). Total S-T segment elevation (sigma ST) in precordial leads V1 to V6 at rest was subtracted from sigma ST at peak stress in order to quantitate the extent of S-T elevation induced by stress (delta ST). Two groups of patients were identified; 1 with stress-induced S-T elevation (Group I, delta ST greater than or equal to 4.0 mm) and 1 without this abnormality (Group II, delta ST less than 4.0 mm). Evidence of abnormal thallium washout from myocardial scan segments occurred in 12 of 15 Group I patients versus 9 of 13 Group II patients (difference not significant). In addition, abnormal tracer washout from anterolateral or septal scan segments occurred in 5 patients in each group. Likewise, abnormal thallium clearance from inferior or posterior scan segments occurred in 8 of 15 Group I patients versus 7 of 13 Group II patients (difference not significant). The patient with the greatest amount of stress-induced S-T elevation (S-T 11.5 mm) had no evidence of ischemia during the stress test. However, Group I patients did have larger anterolateral plus septal initial thallium uptake defect scores than did those of Group II (10 of 15 with defect score greater than or equal to 350 in Group I versus 1 of 13 in Group II, p less than 0.002). Similarly, resting left ventricular ejection fraction greater than or equal to 30% was present in only 4 of 15 Group I patients versus 13 of 13 in Group II (p less than 0.001). Finally, multiple stepwise linear regression analysis demonstrated that delta ST correlated best with the extent of initial anterolateral plus septal thallium uptake defect score (F = 17.3, p less than 0.001) and to a lesser extent with resting ejection fraction (F = 5.2, p less than 0.05) and change in heart rate from rest to peak stress (F = 8.1, p less than 0.01; corrected multiple correlation coefficient = 0.76, p less than 0.001). Thus, in patients with previous anterior MI (1) exercise-induced myocardial ischemia occurs as often with as without S-T segment elevation, (2) myocardial ischemia is not required for the production of stress-induced S-T segment elevation, and (3) stress-induced S-T elevation primarily reflects the extent of previous anterior wall damage and to a lesser extent an increase in heart rate between rest and peak stress.