The old concept of myelin as a metabolically inert membrane has been considerably revised as a result of the discovery of numerous enzyme activities in the isolated membrane. The high degree of purification and low levels of contamination markers leave little doubt that the measured activities are intrinsic to myelin itself. Slightly more than half of the discovered activities involve lipid metabolism. One such enzyme, neutral cholesterol esterase, is myelin-specific, while the rest occur in other subcellular fractions as well as myelin. These include activities involved in synthesis of cerebrosides, phospholipids, and cholesteryl esters; only a few degradative enzymes are presently known. In vivo studies have shown that various substrates utilized by lipid-synthesizing enzymes of myelin can originate in the axon. Six such substrates have been characterized. The possibility exists that these enzymes may be wholly or partially dependent on the axon as the primary source of substrate, thereby suggesting a possible form of metabolic dependency of myelin on the axon.