Saltatory conduction of nerve impulses along axonal membranes depends on the presence of a multilayered membrane, myelin, that wraps around the axon. Myelin basic protein (M BP) and myelin protein 2 (P2) are intimately involved in the generation of the myelin sheath They are also implicated in a number of neurological diseases, including autoimmune diseases of both the central and peripheral nervous systems Here, we have used atomic force microsopy (A FM) to study the effects of M BP and P2 on lipid bilayers. M BP in association with a mica substrate appeared unstructured, and tended to coat the mica surface in the form of a monolayer. In contrast, P2 appeared as discrete particles, with molecular volumes consistent with the formation of both monomers and chillers Either M BP or P2, at micromolar concentrations, caused stacking of brain lipid bilayers This stacking effect was significantly potentiated when both proteins were added together. Mayers composed of phosphatidylcholine (PC) and phosphatidylserine (PS) were stacked by M BP, provided that cholesterol was also present, in contrast, P2 did not stack PC/PS/cholesterol bilayers. Hence, the bilayer stacking effects of the two proteins have different lipid requirements