Previous studies show considerable variation in the perfusion and function of the left ventricle at rest and during stress in patients with disease of the isolated left anterior descending coronary artery. In search of mechanisms, we obtained exercise thallium-201 images in 35 such patients. None of the patients had had infarction. The exercise-induced perfusion defect size was measured as the average of the percentage of abnormal perimeter from the three standard projections. The perfusion defect size was smaller in the nine patients with 50-69% stenosis than in the 26 patients with ≥ 70% stenosis (10 ± 9% vs 27 ± 15%, mean ± SD, p < 0.01). Among the 26 patients with ≥ 70% stenosis, the perfusion defect was ≤ 30% in 14 and > 30% in 12. All 14 patients with perfusion defects ≤ 30% were older than 50 years; eight of the 12 with perfusion defects > 30% were 50 years of younger (p = 0.0003). The severity and site of stenosis, collaterals, exercise heart rate and double product, propranolol therapy and results of exercise ECG were similar in patients with perfusion defects ≤ 30% and in patients with perfusion defects > 30%. Using a stepwise regression analysis of 30 clinical, anatomic and exercise variables, only age showed a significant correlation with perfusion defect size (r = -0.58, p < 0.005). In patients with effective collaterals, the perfusion defect was smaller in patients older than 50 years than in patients age 50 years or younger (14 ± 7% vs 41 ± 8%, p < 0.001). We conclude that the perfusion defect is small in patients with < 70% stenosis of the left anterior descending coronary artery, but varies considerably in patients with ≥ 70% stenosis. Age is the chief determinant of perfusion defect size in patients with similar left anterior descending coronary artery anatomy and exercise variables. Age and, conceivably, the duration of disease may affect the functional maturity of collaterals. The data indicate that left anterior descending coronary artery lesions may well put into risk more than 30% of the heart muscle in a great number of patients. This phenomenon is significantly more common in patients younger than age 50 years.