The effect of environmental ion concentration on the enzyme activity of astrocytes was investigated in tissue cultures of rat cerebral cortex. It was found that the oxidative enzymatic activity (succinic dehydrogenase, DPN-diaphorase, and several other enzymes) of astrocytes depended on the concentration of NaCl in the environment. This response was not specific for NaCl, but was also elicited by MgCl(2) and LiCl; the response was less consistent, and often questionable for KCl. However, only NaCl could elicit enzymatic changes in astrocytes at concentrations known to be present in a living organism. Astrocytes were the only cells which responded this way; it appeared that the foot-plates were particularly involved in the response since increase of enzyme activity occurred earlier in the foot-plates than in the perikarya. It was concluded that astrocytes are metabolically involved in the maintenance of the ionic and osmotic environment of the central nervous system, particularly in regard to the active transport of sodium.