Macrophages are in large part responsible for the subendothelial deposition of lipid within the artery wall during the early stages of atherogenesis. Proteoglycans secreted by these cells may play a role in this pathological process either by trapping lipoproteins in the extracellular matrix or by enhancing the formation of lipid-laden foam cells. The synthesis and secretion of proteoglycan was studied in the P388D1 macrophage-like cell line cultured in the presence of 35S-sulfate. The radiolabeled proteoglycan had a Kd of 0.69 on Sepharose CL-2B corresponding to an Mr of 2.8 x 10(5). It consisted of approximately 13 chondroitin sulfate chains of Mr 20,000 attached to a core protein with an Mr of 18,000. The chondroitin sulfate chains contained both N-acetylgalactosamine 6-sulfate and N-acetylgalactosamine 4-sulfate residues. No disulfated N-acetylgalactosamine residues were present. The P388D1 proteoglycan bound specifically to immobilized human low density lipoprotein. These results suggest that, in the focal regions of the arterial wall in which macrophages are found during the development of fatty streaks, proteoglycans secreted by these cells may affect the transport and cellular metabolism of plasma-derived lipids.