To determine the prevalence of septal defects in a generalized referral population, the records of 93 consecutive patients with complete left bundle branch block (BBB) who underwent symptom-limited treadmill exercise testing with thallium-201 myocardial imaging over a 3-year period were reviewed. Segmental analysis of the planar thallium-201 images was performed in a blinded fashion with agreement by consensus. Computerized quantitative analysis of the images also was independently performed, and was correlated with the visual interpretations. Forty-seven patients (51%) had normal images, and 46 (49%) had defects of greater than or equal to 2 segments. In the abnormal studies, only 13 patients (14% of the total population) had septal defects, while a much higher number of patients, 33 (39%), had inferior or apical defects, or both. Coronary angiography was performed in 6 patients with septal defects: Significant narrowing of the left anterior descending coronary artery was found in 4 patients, a narrowed right coronary artery was found in 1, and normal coronary arteries were seen in the other patient. In conclusion, whereas previous studies have suggested a high percentage of false-positive septal defects in patients with left BBB, this study demonstrates a low prevalence (14%) of septal defects in a large population of unselected patients presenting for exercise thallium-201 imaging. Therefore, exercise thallium-201 imaging remains a useful procedure for evaluating patients with complete left BBB.