The conformation studies of myelin P2 protein and two of its major peptides were carried out using circular dichroism and fluorescence spectroscopy in water and in lipid environments. Significant conformational changes occur when the protein or peptides were bound to gangliosides. Similar effects were also found in trifluoroethanol solutions. The conformational features of P2 protein and its major peptides were discussed in relation to the environmental changes and the disease-inducing effects.