In the fetal rat hypophysis, the "opio-melano-corticotropic" cells were immunocytologically revealed earlier in the pars distalis (day 16) than in the pars intermedia (day 17). At an early stage of embryonic development, some factors, possibly of nervous origin, could exert inductive influence on the differentiation and/or the increase in the number of immunoreactive cells. 2. Several forms of ACTH, characterized by their apparent molecular weight, bioactivity and immunoreactivity, can be observed when acid extracts are subjected to gel filtration on Sephadex G 50 fine columns. The ratios between these ACTH forms change during fetal development; the rise in bioactive ACTH content during the last days of gestation, is correlated with an increase of the "intermediate" and "little" molecular forms of ACTH and a parallel decrease of the "big" form. 3. The hypophyseal corticotropic activity is highest on days 18-19 of gestation. Between days 17 and 19, the cortico-stimulating activity is largely independent of the hypothalamus although the fetal hypothalamus shows light hypophyso-stimulating influence. In contrast, between days 19 and 21, the hypophyseal corticotropic activity is mostly under the hypothalamic control; the ACTH release is greatly reduced in its absence. 4. Circulating corticosteroids exert a negative feedback directly at the hypothalamic and pituitary levels. Such negative feedback could explain the decrease of the corticotropic activity of the pituitary during the last three days of gestation and the first postnatal days. 5. The fetus at the end of gestation, as the newborn, is responsive to stress; however, the extent of the pituitary response is weaker than in the adult.
