The relationship between odontoblasts and class II major histocompatibility complex (MHC) antigen-expressing cells in the process of dentinogenesis was studied in rat lower incisors, employing immunohistochemistry using OX6-monoclonal antibody. The dental pulp contained numerous OX6-immunopositive cells that varied in morphology from dendritic to spindle under physiological conditions. Under the electron microscope, these immunopositive cells shared common cytoplasmic features, i.e., multivesicular bodies and characteristic fine tubulovesicular structures in their cytoplasm. At the early stage of dentinogenesis, OX6-immunopositive cells, presumably of the immature type, were located in the subodontoblastic layer. During active dentin formation, the OX6-immunopositive cells increased in number and appeared in the odontoblast layer, associating intimately with fenestrated capillaries situated close to the predentin. These cells showed a dendritic appearance and possessed various sizes of multivesicular bodies and characteristic fine tubulovesicular structures, but never contained typical phagosomes. On the other hand, immunopositive macrophages characterized by typical phagosomes tended to occupy the central portion of the pulp. The results suggest that most, if not all, OX6-immunopositive cells situated deep in the odontoblast layer are dendritic cells playing a role in the defense system of the dental pulp against antigenic molecules arriving from the circulation via the fenestrated capillaries. The increasing number of OX6-immunopositive or immunonegative macrophages appearing near the incisal end of the tooth is thought to be involved in the elimination of degenerated odontoblasts.