To examine the susceptibility to myocardial ischemia with mental stress in patients who have coronary artery disease and normal left ventricular (LV) function versus those who have impaired LV function, we examined 58 patients who had coronary artery disease, including 22 who had normal LV function (ejection fraction >/=50%), 16 who had mild to moderate LV dysfunction (ejection fraction 30% to 50%), and 20 who had severe LV dysfunction (ejection fraction </=30%) and underwent bicycle and mental stress testing with myocardial perfusion scintigraphy on consecutive days in random order. Ischemia was assessed based on summed difference scores in regional rest versus stress myocardial perfusion and defined as a summed difference score >3. At comparable double products across the 3 groups, ischemia was induced with mental stress more frequently in patients who had severe LV dysfunction (50%) than in those who had normal LV function (9%; p <0.01). The frequency of exercise-induced ischemia was different only between those who had mild/moderate LV dysfunction and those who had normal LV function (56% vs 18%, respectively, p <0.05). The pattern of mental stress versus exercise ischemia differed between groups (p <0.02): there was a higher prevalence of mental stress ischemia versus exercise ischemia in patients who had severe LV dysfunction (p = 0.06), a marginally higher prevalence of exercise versus mental stress ischemia in those who had moderate LV dysfunction (p = 0.07), and no difference in mental stress versus exercise ischemia in those who had normal LV function. Thus, at comparable double products during mental stress and similar extent of coronary artery disease, ischemia with mental stress was induced more frequently in patients who had severe LV dysfunction than in those who had normal LV function. These data suggest that mental stress ischemia may be of particular clinical importance in patients who have coronary artery disease and LV dysfunction.