Macrophages that rapidly enter injured peripheral nerve synthesize and secrete large quantities of apolipoprotein E. This protein may be involved in the redistribution of lipid, including cholesterol released during degeneration, to the regenerating axons. To test this postulate, apolipoprotein E-associated lipid particles released from segments of injured rat sciatic nerve and apolipoprotein E-containing lipoproteins from plasma were used to determine whether sprouting neurites, specifically their growth cones, possessed lipoprotein receptors. Pheochromocytoma (PC12) cells, which can be stimulated to produce neurites in vitro, were used as a model system. Apolipoprotein E-containing lipid particles and lipoproteins, which had been labeled with fluorescent dye, were internalized by the neurites and their growth cones; the unmetabolized dye appeared to be localized to the lysosomes. The rapid rate of accumulation in the growth cones precludes the possibility of orthograde transport of the fluorescent particles from the PC12 cell bodies. Thus, receptor-mediated lipoprotein uptake is performed by the apolipoprotein B,E(LDL) (low density lipoprotein) receptors, and in the regenerating peripheral nerve apolipoprotein E may deliver lipids to the neurites and their growth cones for membrane biosynthesis.