EDTA treatment of post-natal mouse molars made possible the isolation of cell-free dental matrices composed of basal lamina, predentin, dentin and enamel. Trypsin-isolated dental papillae and enamel organs from embryonic-mouse mandibular molars were combined with isolated matrices and cultured in vitro. In such recombinations, functional odontoblasts were never observed. On the other hand, competent preameloblasts in contact with the epithelial side of occlusal predentin overtly differentiated. Matrices treated with guanidine-EDTA or acetic acid were unable to promote the functional differentiation of ameloblasts. These data are discussed in terms of the epitheliomesenchymal interactions involved in odontogenesis.