Major depression is common in patients with coronary artery disease (CAD)and is associated with significantly increased cardiac morbidity and mortality in these patients. The mechanism for this effect is unknown, but altered autonomic tone is the most plausible candidate. The primary objective of the proposed research is to extend our previous studies of this putative mechanism. Patients who are found to have clinically significant CAD on elective cardiac catheterization and who screen positive for depression will receive a structured psychiatric interview. Patients who meet the DSM-III-R criteria for a current major depressive episode will be matched with the next same-sex nondepressed patient in the series who has comparable disease severity and who is approximately the same age (+ 3 years). Twenty-four hour urinary catecholamine and thromboxane B2 levels, heart rate variability, and catecholamine response to orthostatic testing will be determined for all subjects. The subjects will then undergo standard exercise testing (ET) on a bicycle ergometer in order to determine the time to onset of myocardial ischemia. Plasma catecholamine levels will be determined at rest and at the onset of 1mm ST segment depression. Depressed and nondepressed patients will be compared on these variables. Depressed patients will then be treated with cognitive therapy for four months. After four months, both groups will be reinterviewed and all tests will be readministered. Pre-post treatment comparisons of catecholamine response during orthostatic testing and during exercise, time to myocardial ischemia on the ET, as well as heart rate variability and 24 hour urinary catecholamine and thromboxan B2 levels, will be compared between those patients whose depression is in remission and those matched controls who remain free of depression. The results of this study should clarify the role of altered autonomic tone in reducing the threshold for myocardial ischemia in cardiac patients with major depression, and provide data concerning the effects of treating depression on autonomic tone and ischemic threshold.