Previous angiographic observations have characterized transplant atherosclerosis as a generally diffuse and more distally severe disease with obliteration of secondary branches. However, it has not been firmly established that the disease is structurally and biologically more severe distally. We evaluated this hypothesis with computer-based digitization of subserial segments of the entire perfusion-fixed left anterior descending coronary artery (100 mm Hg for 1 hour with 10% formaldehyde solution) in 25 allografts at autopsy or explant (19 male and 6 female patients; mean age = 50 years, range 16 to 66; mean implant duration = 490 days, range 3 to 1610). The area, thickness, circumference of the intima and media, and the relative and absolute luminal narrowing were evaluated in a mean of 10 left anterior descending coronary artery sections per allograft. The percentage of luminal narrowing (intimal area/[intimal area + luminal area] x 100) was similar between proximal and distal segments of the left anterior descending coronary artery (45% versus 41%, p > 0.05), and the mean absolute intimal thicknesses (in millimeters) of proximal and distal segments of the left anterior descending coronary artery also were not different (0.32 versus 0.22, p > 0.05). In addition, the 95% confidence intervals for intimal thicknesses of proximal and distal segments were comparable. Because the absolute arterial size of proximal segments is naturally larger than that of distal segments (external diameter 9.37 versus 6.79, p < 0.0001), an appearance of progressive tapering may be visualized angiographically, even though the biologic severity of the disease is geographically uniform. Similarly, observations of obliterated secondary branches in distal segments may result from naturally smaller distal luminal areas which may be occluded by less intimal thickening than would be required proximally. These data emphasize that transplant atherosclerosis is biologically uniform from proximal to distal locations. Etiologic and pathogenetic studies on proximal or distal segments should be equally informative.