The effect of the atypical neuroleptics clozapine and risperidone, the potential atypical neuroleptics sertindole and NNC 22-0031 as well as the prototypical neuroleptic haloperidol on Fos protein expression in the rat forebrain was examined by use of immunohistochemistry. Fos protein expression in the limbic medial prefrontal cortex (PFC) relative to Fos protein expression in the non-limbic dorsolateral striatum (DLSt) was more pronounced for the atypical and potential atypical neuroleptics than observed with the prototypical neuroleptic, indicating that atypical and prototypical neuroleptics can be differentiated on the basis of their ability to induce Fos protein in these regions.