In situ hybridization and immunohistochemistry were used to examine the expression of c-fos, Hsp70 and Hsp27 following photothrombotic injury in the right fronto-parietal cortex of the rat. C-fos mRNA and protein were detected in the entire cerebral cortex on the lesioned side. Hsp70 mRNA accumulation was observed only adjacent and peripheral to the site of the lesion. At 1 h after photothrombotic injury, Hsp70 expression delineates the area of necrosis at 24 h after photothrombotic injury. Hsp27 protein was observed in the ipsilateral cerebral cortex with the exception of the deep layers of the cingulate cortex. In addition, while c-Fos immunoreactivity was localized in cell nuclei, Hsp27 immunoreactivity was detected in the cytoplasm of astrocytes. These results demonstrate that unilateral cortical injury induces changes in gene expression that vary according to cell type and brain region.