Acute mental stress may be a frequent trigger of transient myocardial ischemia, myocardial infarction and sudden cardiac death. In an experimental setting, the effect of mental stress on hemodynamics and left ventricular wall motion abnormalities (as detected by radionuclide ventriculography) was measured in 29 patients with exercise-induced myocardial ischemia. Seventy-five percent of the patients demonstrated mental stress-induced wall motion abnormalities. Patients frequently exhibited greater increases in peak systolic arterial pressure during mental stress than during exercise. Personally relevant mental stress is the most potent type of mental stress, both in terms of frequency and magnitude of ischemia. Most mental stress-induced ischemic episodes are clinically and electrocardiographically silent and occur at heart rates significantly lower than those seen during exercise. Both systolic and diastolic blood pressure increased during mental stress-induced ischemia, suggesting that increased myocardial oxygen demand plays a role in the pathophysiology of mental stress-induced transient ischemia. The significant magnitude and acute onset of this mental stress-induced blood pressure elevation may in some manner contribute to atherosclerotic plaque rupture. These findings may provide a pathophysiologic link to the epidemiologic association between mental stress and acute ischemic coronary events. A new ambulatory radionuclide detector that can concurrently monitor left ventricular ejection fraction and electrocardiographic ST-segment change may enhance the detection and evaluation of transient myocardial ischemia in ambulatory coronary patients.