It has been shown by immunohistochemical studies that alpha B-crystallin accumulates in the reactive and neoplastic glial cells in a variety of pathologic situations. However, the molecular mechanism for the induction of alpha B-crystallin in diseased brains is still unknown. Since any destructive brain lesions cause an abnormal elevation in the potassium (K+) concentration of the extracellular space, which disturbs the regulatory mechanism of glial cell volume, we investigated the influence of elevated extracellular K+ on the expression of alpha B-crystallin in glial cells. The treatment of rat C6 glioma cells with augmented K+ in the culture media induced an accumulation of alpha B-crystallin mRNA in a dose-dependent manner and an accumulation of the alpha B-crystallin as well. Furthermore, an overexpression of alpha B-crystallin in the C6 transformant transfected with a rat alpha B-crystallin cDNA conferred a resistant phenotype against the insult of elevated extracellular K+ on the glioma cells. Thus, alpha B-crystallin may contribute to the survival of reactive glia in the presence of a high extracellular K+ concentration.