The usefulness of exercise electrocardiography (ECG) and myocardial stress perfusion scintigraphy (SPS) in the noninvasive identification of patients with left main or three-vessel coronary artery disease (CAD) was assessed. Ninety-six patients with chest pain were divided into three groups. Group I consisted of 44 patients with left main or three-vessel CAD. Group 2 included 37 other patients with CAD. Group 3 comprised 15 patients with normal coronary arteries. Standard criteria for positive and nondiagnostic SPS and ECG were used. Markedly positive patterns of SPS and ECG suggestive of left main or three-vessel CAD were defined. Forty-two (95%) group 1 patients had positive SPS and 28 (64%) had positive exercise ECG (p < 0.005). Twenty-four (65%) group 2 patients had positive SPS (p < 0.005 compared with group 1) and 14 (38%) had positive ECG (p < 0.05 compared with group 1). No group 3 patient had a positive SPS and three (20%) had positive ECG. Markedly positive SPS and ECG each detected only 19 (43%) and 15 (34%) group 1 patients, respectively. ECG or SPS were markedly positive in 30 (68%) group 1 patients, significantly increasing the diagnostic yield (p < 0.005). The specificity of markedly positive SPS (95%) for left main or three-vessel CAD was higher than markedly positive ECG (86%), but not statistically different. SPS is more sensitive than ECG for the diagnosis of CAD in patients with left main or three-vessel CAD. However, SPS and ECG have low sensitivity for the accurate identification of this subgroup of patients with high-risk anatomy. Two scintigraphic patterns have been characterized that are specific for left main or threevessel CAD. These patterns, in conjunction with ECG, allow noninvasive identification of 68% of symptomatic patients with left main or three-vessel CAD.