Wide-angle x-ray diffraction studies revealed that the lipid-phase transition temperature of multiple sclerosis (MS) myelin was about 20°C lower than that of normal myelin, indicating differences in the physical organization of the bilayer. The transition temperature of liposomes prepared from total lipid extracts of normal myelin was 12°C lower than that for corresponding intact myelin, demonstrating that the protein of normal myelin had a substantial ordering effect on the lipid bilayer. The transition temperature for liposomes of MS myelin lipid was essentially similar to that for isolated MS myelin. Because the protein/phospholipid ratio was higher in MS myelin, and no difference in degree of fatty acid saturation was observed, the inability of MS myelin protein to organize the lipid reflects a qualitative difference in the proteins.Multiple sclerosis (MS) is a demyelinating disease affecting primarily the white matter of the central nervous system (1, 2). Demyelination occurs in discrete plaques found throughout the white matter of the brain (3, 4). Consequently, the disease has been considered to be one with multiple foci of discrete demyelination.There remains the possibility, however, that there is a more generalized involvement of white matter in the pathology of MS. In a recent low-angle x-ray diffraction study in which long-chain fatty alcohols were incorporated into myelin, the presence of additional reflections in the MS samples implied that the alcohols formed regular structures in domains of disorganized bilayer (5). Boggs and Moscarello (6) have shown an increased protein/lipid content in MS myelin but were unable to detect any significant difference in membrane fluidity by using fatty acid spin labels or fluorescent probes. Recently, however, an x-ray diffraction study re-vealed that basic protein from MS myelin was much less effective in inducing lipid organization in egg phosphatidylglycerol vesicles in comparison with basic protein from normal myelin (7). As well, the formation of the characteristic multilayer arrangement has been shown to depend on the concentration of basic protein because sharp reflections were observed by x-ray diffraction only when the concentration of basic protein was 30% (wt/wt) in the basic proteinphosphatidylglycerol system (8), supporting an earlier report in which digestion by trypsin disrupted myelin structure (9).The present study focuses on alterations in biophysical and chemical changes in myelin due to the neuropathology of MS.