Alpha-Crystallin is a major eye lens protein, composed of two types of subunits, alpha-A and alpha-B. The alpha-A subunit is restricted to the lens, but alpha-B-crystallin has recently also been detected in non-lenticular tissues, including the nervous system. With the use of a polyclonal antiserum directed against a synthetic C-terminal peptide of human alpha-B-crystallin, the presence of alpha-B-crystallin could be demonstrated immunohistochemically in astrocytes in the brains of patients with Creutzfeldt-Jakob disease (CJD). Most intensive localization was observed in the spongiotic tissue representing abundant progressively changed astrocytes in CJD. In age-matched control brains weak positive reaction was located in individual oligodendroglia cells and subpial astrocytes. Prominent increase of alpha-B-crystallin in pathological glia in CJD may represent a response to stress.