We have previously shown that antisera to whole CNS myelin, whole PNS myelin, galactocerebroside (GC), and myelin basic protein (MBP) promote the uptake of CNS myelin by cultured macrophages, and stimulate the conversion of myelin lipids to cholesterol ester and triglycerides. Here we report the results of similar studies using PNS myelin purified from the rat sciatic nerve. Antisera to whole CNS myelin, whole PNS myelin, GC, and MBY preincubated with 14C-labeled PNS myelin increased the production of radioactive cholesterol ester by macrophages in culture to a level about twice that with preimmune serum, and five to six times that of untreated myelin. The amounts of ['4C]triglyceride were similarly increased with these antisera, whole Po and P, antisera had little or no effect. IgG prepared from the antisera stimulated lipid metabolism to almost the same extent, while heating the antisera did not decrease the stimulatory effect, indicating that myelin was opsonized by IgG, but not likely by complement. With a few exceptions, the four active sera and their IgGs promoted the macrophage metabolism of CNS and PNS myelin almost equally. The cultured macrophages converted about 3% of untreated CNS myelin and about 6% PNS myelin cholesterol to cholesterol ester. Under phase contrast microscopy it was noted that vesicles of CNS myelin appeared to bind individually to macrophages, whereas PNS myelin vesicles tended to self-associate to form large clumps which were bound to macrophages. Binding studies showed PNS myelin to be bound more firmly to macrophages than CNS myelin. The presence of high amounts of glycoprotein in PNS myelin may account for this difference in binding to macrophages, either through self-adhesion of the PNS myelin particles, or by the presence of carbohydrate receptors in macrophages. These results may define a role for antibody in myelin destruction in cell-mediated demyelinative diseases, and may be relevant to the differences seen in vivo between the rates of demyelination of peripheral and central nerves.