The size of the perfusion defect was assessed from a quantitative analysis of exercise thallium-201 images. Quantitative analysis was determined by measuring the area and the perimeter of the perfusion defect and expressing it as a percentage of the total left ventricular area or perimeter in three projections. Using this technique, we studied 50 patients with one-vessel disease of 50% or greater diameter narrowing. The planimetric and the perimetric methods correlated well (p < 0.001, r = 0.97). Of the 11 patients with less than 70% diameter narrowing, only one patient had abnormal exercise thallium-201 images. Of the remaining 39 patients with 70% or greater diameter narrowing, 35 had abnormal exercise images. The defects were larger in patients with left anterior descending coronary artery disease (33 ± 10%; mean ± SD by perimetry) than in patients with left circumflex coronary artery disease (19 ± 14%, p < 0.01) or right coronary artery disease (17 ± 11%, p < 0.01). There was also significant variation in the sizes of the defects in the three projections in patients with left circumflex and right coronary artery disease, but not in patients with left anterior descending coronary artery disease. Patients with left anterior descending coronary artery disease with collaterals had smaller defects than their counterparts without collaterals (25 ± 6% vs 40 ± 8%, p < 0.001). We conclude that in patients with one-vessel disease, the quantitative size of the perfusion defects during exercise is highly variable. Patients with left anterior descending coronary artery disease have larger defects than patients with left circumflex or right coronary artery disease. The significantly lower quantitative thallium scores in patients with left anterior descending coronary artery disease and collaterals suggest that collaterals have a protective role during exercise in these patients.