The distribution of the proto-oncogene product, c-fos protein, has been studied in tissue from adult rat brain using immunocytochemical techniques. Sections of rat brain were incubated with a polyclonal antibody to a synthetic fragment of the c-fos protein (M-peptide) and visualized for immunoreactivity using the avidin-biotin technique. Low levels of c-fos protein-like immunoreactivity were concentrated in the nucleus. Dark nuclear staining of cells was observed in the cerebral cortex, in hippocampal pyramidal neurons, in granule cells of the dentate gyrus and other regions. Neurons in the cat visual cortex also showed low levels of c-fos protein-like immunoreactivity. Pre-absorbing the antibody with the M-peptide abolished the immunostaining. Generalized seizures evoked by injection of pentylenetetrazol produced a massive induction of fos protein(s) in the piriform and cingulate cortices as well as the dentate gyrus of rats. These results demonstrate that c-fos protein-like immunoreactive material is found within the nuclei of fully differentiated adult mammalian neurons at low basal levels and that activation of nerve cells leads to an induction of c-fos proteins.