In order to clarify the environmental factors which are involved in the development of the primordium of the pituitary gland such as cell-cell interactions, a three-dimensional reconstruction of this organ and its surrounding tissues was carried out. Pituitary material was obtained from human fetuses mainly during the period of organogenesis. Rathke's diverticulum was found to stretch rostrally from the stomodeal epithelium to the middle of the mesoderm, and already by the 5th week of fetal growth, it was clearly seen to be involved with the diencephalon. The area of contact between Rathke's pouch and the diencephalon gradually moved from the rostral to caudal regions and, after 13 weeks of development, had a position similar to that found in the newborn infant. Among the cells forming Rathke's pouch, it was found that the closer their relationship was to the diencephalon, the greater were their epithelial characteristics. When the relationship of such cells to the diencephalon was weaker, their differentiation to endocrine cells occurred earlier. Immunohistochemically, that portion of the pituitary primordium which has a close relationship with the diencephalon, later to become the pars intermedia, showed an adrenocorticotropic hormone (ACTH) immunoreactivity later than that of the pars anterior. On the other hand, in the 21st fetal week, nearly all of the cells of the pars intermedia were found to be ACTH-positive. This finding is thought to indicate a close connection between the physical contact between the brain (diencephalon) and the pituitary primordium and the development of the pars intermedia; the differentiation of ACTH cells. The surface of the epithelium of Rathke's cavity continues to increase at least until the 21st fetal week, so the growth of the epithelium of Rathke's pouch is thought to be heavily involved in the growth of the primordium of the pituitary gland in the early stages of development.