This study investigated the hypothesis that increased influx of low-density lipoprotein (LDL) accounts for the natural development of atherosclerosis in a characteristic (susceptible) site in the distal thoracic aorta of White Carneau (WC) pigeons and the exacerbation of atherosclerosis by cholesterol feeding. The influence of dietary cholesterol-induced changes in LDL composition on LDL influx into the artery was also investigated. As a measure of the influx of LDL into the artery, we determined the arterial accumulation of radiolabeled LDL after 1 hour. Nine 50-month-old WC pigeons with naturally occurring atherosclerosis and seven 14-month-old WC pigeons with atherosclerosis accelerated by 10 months of cholesterol feeding were studied. In the absence of atherosclerotic lesions, we found no evidence for increased accumulation of LDL at the susceptible site. In fact, more LDL accumulated in less susceptible normal arterial areas near the heart (=90 nl/h per square centimeter) than in the susceptible distal thoracic aorta (»35 nl/h per square centimeter). In the absence of atherosclerotic lesions, LDL accumulation (nanoliters per hour per square centimeter) was not influenced by hypercholesterolemia, although mass transport of LDL cholesterol into the artery was increased. Naturally occurring atherosclerotic lesions accumulated five times as much LDL as the adjacent normal arterial area (p<.001), whereas cholesterol-aggravated atherosclerotic lesions in different arterial sites accumulated four to 26 times as much LDL as the adjacent normal artery (p<.05). Cholesterol-aggravated atherosclerotic lesions at the most susceptible site accumulated five times as much LDL as naturally occurring atherosclerotic lesions in the corresponding arterial site (823±241 vs 175±45 nl/h per square centimeter, mean±SEM;p<.005). Arterial accumulation of LDL was influenced very little by changes in LDL composition induced by cholesterol feeding. In another study with young WC pigeons free of atherosclerosis and other WC pigeons with cholesterol-aggravated atherosclerosis, we injected differently labeled LDL 0.5 and 1 hour before sacrifice to investigate whether efflux of LDL from the artery was significant during a 1-hour period of LDL uptake. Although efflux of LDL from all arterial sites occurred during 1 hour, differential efflux could not account for regional differences in 1-hour arterial LDL accumulation. This study suggests that the characteristic susceptibility of the distal thoracic aorta of WC pigeons to atherosclerosis and the exacerbation of atherosclerosis by cholesterol feeding cannot be explained by differences in influx or efflux of LDL. Apparently, susceptibility to atherosclerosis in WC pigeons is determined by differences in other processes, such as metabolism of LDL after entering the artery or efflux of cholesterol from arterial cells.