To evaluate the relation of mental stress-induced ischemia to silent ischemia on ambulatory monitoring, 46 patients with stable coronary artery disease underwent standardized laboratory mental stress and exercise treadmill testing according to National Institutes of Health protocol during which left ventricular ejection fraction (EF) was determined using the nuclear VEST. Life stress, type A behavior, and hostility were determined using standard interviews. Subsequently, 48-hour ambulatory electrocardiographic monitoring was performed. Twenty-three patients (50%) had an ischemic response (left ventricular EF decrease > or = 5%) to mental stress, which was associated with ambulatory ischemia (13 of 19 with ambulatory ischemia had mental stress-induced ischemia vs 10 of 27 without ambulatory ischemia, p = 0.04). Left ventricular EF response to mental stress was a significant predictor of ambulatory ischemia independent of EF response to exercise (F = 4.8, p = 0.03). Patients with mental stress-induced ischemia had longer total duration (31.4 +/- 57.0 vs 8.3 +/- 18 minutes, p = 0.06) and more frequent episodes of ambulatory ischemia (3.1 +/- 4.6 vs 0.9 +/- 1.9 episodes, p = 0.03). Life stress, type A behavior, and hostility were not associated with prevalence or severity of ambulatory ischemia. In conclusion, an ischemic response to mental stress is significantly associated with higher prevalence, longer duration, and more frequent episodes of ambulatory ischemia.