We have previously shown that alpha B-crystallin is a heat-shock protein which specifically accumulates in response to the expression of c-Ha-ras and v-mos oncogenes in mouse NIH 3T3 fibroblasts. Elevated levels of alpha B-crystallin mRNA or protein were shown to be associated with pathological conditions of the brain. Therefore, we have examined the expression of alpha B-crystallin in normal human brains and brain tumors by Western blot analysis. alpha B-crystallin is moderately expressed in adult but not fetal brain. Elevated levels of alpha B-crystallin expression are observed in glial tumors such as astrocytoma, glioblastoma multiforme, and oligodendroglioma. alpha B-crystallin in these tumors is predominately unphosphorylated. High amounts of accumulated alpha B-crystallin in astrocytic tumors are preferentially found in the more aggressive stages. Glioblastoma multiforme is exceptional in that high alpha B-crystallin expression is observed in only one half of the analyzed samples whereas no alpha B-crystallin could be detected in the other. These results indicate that alpha B-crystallin may be a useful biochemical marker for studying the pathogenesis of various human brain tumors.