Cultures of glial cells consisting predominantly of oligodendrocytes and astrocytes were prepared to study whether the biosynthesis of carnosine (beta-Ala-His) and the cellular uptake of this dipeptide are processes which are associated with a specific cell type. Uptake of the radiolabeled precursor beta-alanine was observed in both cultures. Synthesis of radiolabeled carnosine, however, was only observed in oligodendrocyte cultures prepared from rat brain and spinal cord. During oligodendrocyte cultivation we observed a significant increase in the rate of carnosine synthesis which correlates with the differentiation of these cells as revealed by immunostaining with antibodies against oligodendrocyte markers. Carnosine synthesis was not observed in astroglia cell cultures that were depleted of residual O2-A progenitor cells and oligodendrocytes by antibody mediated complement cell killing. Contrary to the synthesis, carnosine was found to be taken up effectively only by astrocytes but not by oligodendrocytes.