Episodes of psychological and physical stress may elicit thrombotic cardiac events, such as myocardial infarction. These events are triggered when there are concurrent hemodynamic, hemostatic, and endothelial abnormalities. Hemodynamic, hemostatic, and endothelial reactions of 72 (15 women, 57 men) coronary artery disease patients to psychological and physical stress were examined. Blood pressure, electrocardiography, and impedance cardiography were recorded during rest, mental arithmetic, and exercise. Blood was collected, via catheter, at rest and after each task. Mental arithmetic elicited increases in blood pressure, heart rate, cardiac output, and cardiac contractility, but no consistent changes in hemostatic and endothelial markers. In contrast, exercise, in addition to increasing blood pressure, heart rate, cardiac output, cardiac contractility, and lowering peripheral resistance, elicited increases in plasma viscosity, hematocrit, platelets, and tissue plasminogen activator together with a decrease in plasminogen activator inhibitor. This pattern of hemodynamic, hemostatic, and endothelial reactions suggests that acute psychological and physical stress influence the thrombotic system differently in these high risk patients. Future research is needed to investigate how these stress responses are prospectively related to acute cardiac events.