The expression of protein kinase c gamma (PKC gamma) and c-fos protein was examined by means of double labeling in the rat brain in relation to the molecular mechanism of central plastic changes associated with anodal polarization. Under normal, non-polarized condition, approximately 75% of all fos positive neurons in the neocortex were immunopositive for PKC gamma. Conversely, nearly all PKC gamma positive neurons were fos immunopositive. Although both pyramidal and non-pyramidal neurons express both types of protein, the pyramidal cell type represents the vast majority. An anodal direct current of 3.0 microA for 30 min to the surface of the left sensorimotor cortex resulted in a pronounced increase in the intensity of immunoreactivity for both PKC gamma and c-fos protein ipsilateral to the polarization. Approximately, 91% of fos positive neurons in the polarized neocortex was also intensely immunoreactive for PKY gamma. The high degree of codistribution of both transduction proteins in specific neurons following anodal polarization suggests the functional connection between PKY gamma activation and c-fos expression in polarization phenomenon.