The usefulness of an abnormal blood pressure response and a marked ischemic ST-segment depression during exercise testing as predictors of severe coronary artery disease was assessed in 378 consecutive patients who had a maximal symptom-limited exercise test before coronary arteriography. An abnormal blood pressure response occurred in 90 patients. The sensitivity of this response for three-vessel or left main disease was 38.6%, the specificity 87.4% and the predictive value 70%. A marked ischemic ST-segment abnormality (MIST) appeared in 85 patients. The sensitivity of MIST for three-vessel or left main disease was 38.6%, the specificity 89.8% and the predictive value 74.1%. One hundred thirty-eight patients had either an abnormal blood pressure response or a marked ST-segment change. The sensitivity of either response for three-vessel or left main disease was 56.4%, the specificity 78.6%, and the predictive value 66.7%. Exercise duration and ejection fraction were not significantly different in patients with normal or abnormal blood pressure. We conclude that abnormal blood pressure and marked ischemic ST-segment depression during exercise testing are helpful in identifying a subset of patients with advanced coronary artery disease. The physiologic mechanism for these responses is probably exercise-induced ischemia.