The activities of cyclic nucleotide phosphohydrolase, an enzyme marker for oligodendrocytes, and glutamine synthetase, an enzyme marker for astrocytes, were studied at early (21 to 26) and late (82 to 88) cell passages. The activity of cyclic nucleotide phosphohydrolase was markedly high and that of glutamine synthetase was low in the early passages, but this relation was reversed in the late passages. These findings suggest a "transdifferentiation" of C6 glial cells with passage in culture.