Extracellular signal regulated kinases (ERKs) are a recently cloned family of genes that encode the MAP kinase protein kinases. They are highly expressed in brain and are believed to play an integral role in neural cellular responses to receptor activation. A role for ERKs has been postulated in Alzheimer's disease, where they have been implicated in phosphorylation of tau in neurofibrillary tangles. We explored the neuroanatomic distribution of ERK immunoreactivity in the rhesus monkey brain. The hippocampal formation, especially the mossy fiber zone and the molecular layer of the dentate gyrus are the most heavily immunostained areas. Cerebral cortex is, in general, more intensely stained in the supragranular layers. The caudate, putamen, and substantia nigra contain more immunoreactivity than the claustrum, globus pallidus, or thalamus with the exception of midline thalamic structures. These results suggest a marked regional and laminar distribution of ERKs in the primate brain.