The cellular localization of carnosine-like immunoreactivity was investigated in the adult rat forebrain and in glial cell cultures obtained from newborn rat brain. Using double staining methods, we showed that in vivo carnosine-like immunoreactivity was occurring in a large number of both glial fibrillary acidic protein (GFAP)-positive astrocytes and 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNP)-positive oligodendrocytes. In vitro, the carnosine-immunoreactive staining was restricted to a subpopulation of completely differentiated oligodendrocytes, whereas no reaction was detected in immature oligodendrocytes and in astrocytes. These observations could have profound physiopathological implications considering the role suggested for carnosine and related peptides as endogenous antioxidants, free radical scavengers and anti-glycating agents of the central nervous system (CNS).