The objectives of this study were to compare and contrast indicators of ischemia in a well-characterized group of 196 patients with coronary artery disease, documented angiographically or by verified history of myocardial infarction, and a positive exercise test result. Myocardial ischemia occurs frequently in response to everyday stressors in patients with coronary artery disease. The Psychophysiological Interventions in Myocardial Ischemia study provides a unique opportunity to study neuroendocrine and psychological manifestations of ischemia. Patients with exercise-induced ischemia underwent exercise radionuclide ventriculography and electrocardiographic monitoring and 2 laboratory mental stressors (Speech and Stroop) after being withdrawn from cardiac medications. In addition, 48-hour ambulatory electrocardiograms were recorded during routine daily activities. Patients with a history of angina within the past 3 months reported angina during the bicycle or treadmill test with a much higher frequency than patients without such an anginal history (77% vs 26%). Ejection fraction (EF) responses to the Stroop test were abnormal in 48% of patients with an abnormal EF response to the Speech task, versus 17% in patients with a normal EF response (p <0.01). Seventy-six percent of patients had an abnormal EF response to bicycle exercise. Three indicators of ischemia (ST-segment depression, wall motion abnormality, and EF response) were compared during the same laboratory stressor and across different types of stress tests. Presence of the 3 indicators was only moderately associated during exercise, and only weak or nonsignificant associations occurred among the presence of the 3 ischemic markers during mental stress. Occurrence of the same ischemic markers was moderately associated between the 2 mental stress tasks, but few associations were found between the occurrence of the same ischemic marker during exercise and mental stress. There is a marked heterogeneity of responses to psychological and exercise stress testing using electrocardiography, ambulatory electrocardiography, or radionuclide criteria for ischemia during stress. The heterogeneity may be related to differences in the magnitude or types of physiologic responses provoked and to differences in the sensitivity and specificity of the different tests used to identify ischemia.