A novel microtubule-associated protein, MAP5, is described, whose chemical properties and cytological distribution distinguish it from other known microtubule-associated proteins (MAPs). Its status as a MAP is indicated by the observations that (i) it co-assembles efficiently with microtubules in vitro, (ii) it is localized on microtubules in brain sections by immunogold staining with monoclonal antibody against MAP5 and (iii) immunoaffinity purified MAP5 stimulates tubulin polymerization. Immunoperoxidase staining of brain sections showed that MAP5 is present in neurons throughout the brain and that in them it is evenly distributed throughout axons, dendrites and cell bodies. In this respect it differs from previously described MAPs (1, 2, 3 and tau) which are differentially compartmentalized in brain neurons. MAP5 is not present in axon terminals, dendritic spines or other synaptic elements. It is present at substantially higher levels in neonatal brain than adult and it is more abundant than either MAP1 or MAP2a up to postnatal day 10. The fall in amount of MAP5, from juvenile to adult levels, is completed between postnatal days 10 and 20. This suggests that MAP5 is particularly important in modulating microtubule function during the formation of neuronal processes.