An antibody prepared against purified 200-kDa neurofilament (NF) subunit was found to cross-react with a high molecular weight polypeptide present in rat brain cytoskeletal extracts starting from early postnatal development. This polypeptide was found to be highly concentrated in microtubule preparations and was specifically recognized as the 280-kDa microtubule-associated protein-2 (MAP-2). Our results, besides suggesting the existence of common epitopes between the heavy NF subunit and MAP-2, suggest the possibility of an interaction between two of the most important neuronal cytoskeletal organelles: NFs and microtubules.