Using a monoclonal antibody against the microtubule-associated protein tau we compared the distribution and the biochemical maturation of this protein in hippocampal pyramidal neurons in the rat in tau and in culture. In tissue sections from mature animals tau was localized heterogeneously within neurons. It was concentrated in axons; dendrites and somata showed little or no staining. In hippocampal cultures ranging from 12 h to 4 weeks in vitro tau was present in neurons but not in glial cells, as it is in situ. Within cultured neurons, however, tau was not compartmentalized but was present throughout the dendrites, axons and somata. Immunoblotting experiments showed that the biochemical maturation of tau that occurs in situ also failed to occur in culture. The young form of tau persisted, and the adult forms did not develop. In contrast the biochemical maturation and the compartmentalization of microtubule-associated protein 2 occurred normally in hippocampal cultures. These results show that the biochemical maturation and the intraneuronal compartmentalization of these two microtubule-associated proteins are independently controlled. Despite the non-restricted distribution of tau in hippocampal neurons in culture, and despite the presence of only the immature isoform which has a lessened stimulatory effect on microtubule polymerization, axons and dendrites appear to grow normally and to exhibit appropriate functional properties.