The accumulation of 125I-low density lipoprotein (LDL) into normal and atherosclerotic arterial tissue and cellular uptake in arterial cells were studied in an in vitro perfusion system for rabbit aorta. The accumulation of 125I-LDL in normal tissue could be fitted to an inverse exponential function with an initial influx rate of 1.39 nl/mg wet weight/hour and an equilibration volume of about 2% of the tissue volume. The influx rate into atherosclerotic plaques was about 10 times faster and the equilibration volume, 50 times higher. In atherosclerotic tissue there was a steep concentration gradient between the plaque and the underlying media. The accumulation of 125I-LDL in the media under plaque and in normal tissue adjacent to plaques was similar to that seen in normal tissue. For studies of cellular uptake of LDL a trace label, 125I-tyramine-cellobiose (TC), was used. Normal or atherosclerotic rabbit aorta was perfused in vitro with medium containing 125I-TC-LDL. After perfusion the tissue was digested and the cells were isolated by density gradient centrifugation. Two main cell fractions with characteristics of smooth muscle cells and foam cells, respectively, were obtained. A 70-fold higher uptake was seen in the foam cells. In conclusion, these studies suggest a higher influx rate into atherosclerotic plaques, as well as a high LDL concentration in the plaque, compared with normal tissue or underlying media. We suggest that most of the cellular uptake of LDL in the arterial wall is caused by the foam cells.