Fifty patients with prior transmural myocardial infarction were studied with cardiac catheterization, coronary angiography, and thallium 201 exercise perfusion scintigraphy.Obstructive coronary disease involved two or three vessels in 37 patients. The sensitivity of a positive electrocardiographic test during exercise for detecting multivessel coronary disease was only 40 percent (15/37), and the sensitivity of a reversible defect on (201)Tl perfusion scintigraphy was 48 percent (18/37). The combination of exercise testing and (201)Tl scintigraphy detected multivessel coronary disease in 75 percent (28/37) (P < .05).New perfusion defects occurred in 61 percent (13/21) of patients with inferior myocardial infarction and multivessel coronary disease whereas it occurred in only 35 percent (5/14) of patients with prior anterior infarction and multivessel coronary disease (P < .05).(201)Tl exercise perfusion scintigraphy appears to be more sensitive for detecting significant multivessel coronary disease in the presence of previous inferior infarction compared with previous anterior infarction.Combined graded exercise testing and (201)Tl perfusion scintigraphy can reliably detect the presence of significant multivessel coronary disease after transmural myocardial infarction.