ACTH release in stress, measured by changesin the plasma corticosterone level, was studied in rats 24 h after isolation of the pituitary by surgical ablation of the medial hypothalamus. Injection of E. coli endotoxin or a large dose of formaldehyde induced a significant increase in ACTH release, whereas either sham-adrenalectomy under ether anesthesia or a small dose of formaldehyde did not. Resting as well as stress-induced increases in ACTH release were depressed by dexamethasone pretreatment after the removal of medial hypothalamus. It was concluded that some of the pathways through which E. coli endotoxin and a large dose of formaldehyde release corticotrophin may bypass the medial hypothalamus; and, further, that the feedback action of dexamethasone may exert itself outside the hypothalamus.