The small dermatan sulfate proteoglycan decorin is efficiently internalized by a variety of cells of mesenchymal origin. Decorin-binding receptor proteins of 51 and 26 kDa are involved in this process. Uptake is modulated by highly sulfated heparan sulfate which interacts with the receptor proteins, too. Compared with cultured skin fibroblasts, bovine aortic endothelial cells have a lower capacity for decorin endocytosis whereas their apparent concentration of receptor proteins is even higher. The low internalization rate is attributed to the greater occupancy of receptor proteins by heparan sulfate of the plasma membrane and/or the extracellular matrix. Growth of endothelial cells on Falcon 3090 tissue culture inserts made possible to study decorin uptake from the apical and basolateral membrane, respectively. Decorin uptake was at the limit of detection when the proteoglycan was added to the basolateral compartment. Uptake via the apical membrane was at least as efficient as in monolayer cultures on plastic. The basolateral membrane, however, was enriched in receptor proteins, but also in heparan sulfate proteoglycans. It is, therefore, suggested that endothelial cells are especially involved in the clearance of decorin which is present in blood plasma.