Myelin membrane has been extracted from the brains of individuals who during their life suffered from multiple sclerosis (MS). The thermotropic properties of these membranes and myelin membrane from brains unaffected by neurological disease were measured with a differential scanning calorimeter and compared. Two melting transitions were found, one near 40 degrees and the other near 80 degrees C. The transition at 80 degrees C appears to be due to reversible denaturation of one of the membrane proteins, the proteolipid protein, and that at 40 degrees C, to irreversible melting of the membrane sphingolipids. In MS myelins these transitions often occurred over a greater temperature range, and in many samples two separate melting processes could be clearly seen. The change in the higher temperature melting is evidently caused by a breakdown of proteolipid protein, as a broadened melting transition similar to that seen in MS myelins was also detected in disease-free myelin which had been stored above O degrees C for several months. In addition, infrared spectroscopy showed that the ratio of the carbonyl/amide absorptions of the membrane (determined largely by the ratio of lipid to protein) increased in a sample which had a very ill-defined high-temperature melting. Loss of proteolipid protein from the membrane could account for such a change in the spectrum. The origin of the two-staged melting of the sphingolipids cannot be determined with any certainty at the moment, but it is possible that the range of lipid species which go to make up the membrane sphingolipids is greater in myelin from the MS-affected brains.