Strong expression of class II major histocompatibility (MHC II, Ia) antigens was observed in areas of Wallerian degeneration following either a cryoinjury to the cerebral and cerebellar cortex or unilateral eye enucleation in adult Wistar and Lewis rats. The Wallerian degeneration was disclosed by the Fink-Heimer method but not by routine histological examination. The Ia antigens were localized exclusively to the cells labeled with OX-42 antibody and mistletoe-1 lectin (ML-1) and possessing the morphological identity of microglia. Development of Ia-expressing microglia at the sites of Wallerian degeneration was accompanied by neither tissue permeation of serum components as assessed by immunohistochemistry for autologous albumin nor tissue migration of hematogenous inflammatory cells.