Vascular endothelial growth factor (VEGF) is a major angiogenetic factor in both developmental and wound healing processes. Recent studies have shown the expression of VEGF mRNA in lung, kidney, heart, ovary and various organs. In order to clarify the role of VEGF in developing human tooth germ, the expression of VEGF and VEGF receptors (KDR/Flk-1 and Flt-1) were investigated on the mandibular deciduous central incisors by immunohistochemistry. At fetal 12 weeks, immunoreactivity of VEGF was detected on many cells in the enamel organ, dental papilla and dental follicle. Immunoreactivity of VEGF in the dental papilla at fetal 14 weeks was localized at undifferentiated cells in adjacent inner enamel epithelium. As compared with immunoreactivity of VEGF at inner enamel epithelium, that of preameloblasts was weak at fetal 18 weeks. At fetal 21 weeks, ameloblasts and odontoblasts were positive for and VEGF. Immunoreactivity of KDR/Flk-1 was similar to that of VEGF. However, it was not visible at ameloblasts and odontoblasts. Immunoreactivity of Flt-1 was not detected in tooth germ except endothelial cells penetrating dental papilla and dental follicle. It was localized on stratum intermedium and outer enamel epithelium at fetal 21 weeks. These results suggest that VEGF, KDR/Flk-1 and Flt-1 are involved in the angiogenesis on developing tooth germ. In addition, VEGF, KDR/Flk-1 and Flt-1 may have an important role in the proliferation and differentiaton of ameloblasts and odontoblasts in human tooth germ morphogenesis.