In order to examine the distribution of amelogenin, type IV collagen and fibronectin in tooth germs of rat and human fetus, immunohistochemical studies were carried out. The following antibodies were used: polyclenal antibody against bovine amelogenin, monoclonal antibodies against rat and human type IV collagen and polyclonal antibodies against rat and human fibronectin. Specimens were tooth germs of mandit ular first molar of rats at 1st day after birth and mandibular first incisor of human fetus at 16 to 24 weeks. Immunoreactivity of amelogenin was found from the early stage of secretory ameloblast. Also we found the penetration in predentin and intercellular space of odontoblasts. At the inner enamel epithelium of human fetus, tooth germ was found a scanty immunoreactivity of amelogenin, whereas it was not found in rats. Immunoreactivity of type IV collagen was found in the basement membrane of both tooth germs. After the predentin was secreted at the epithelial-mesenchymal interface, uniform immunoreactivity was founded and when the dentin was produced and the epithelial cells were differentiated into ameloblasts, the immunoreactivity was abundant. Immunoreactivity of fibronectin was found in the basement membrane, mesenchymal cells predentin and mineralized dentin. When the immunoreactivity of type IV collagen was abundant and the penetration of amelogenin was found in predentin, an intense immunoreactivity of fibronectin was found in predentin. These results suggest the possibility that the penetration of amelogenin toward the odontoblasts is related to the mineralization of predentin. In conclusion, these phenomenon was observed in rat and human fetnc tooth germs.