We show that the major membrane protein of central nervous system myelin, proteolipid protein, evolved much more rapidly than it does now more than 300 million years ago. We reason that myelin proteolipid protein evolved rapidly just after its appearance in vertebrates and that its evolutionary rate then gradually decreased. Comparison of the rates between the synonymous and nonsynonymous nucleotide substitutions for the cDNA suggests the possibility that positive selection operated on myelin proteolipid protein at least when it appeared in vertebrates.