SUMMARY: Corticotrophin (ACTH) release induced by stressful stimuli has been studied in rats with completely deafferentated medial basal hypothalamus (MBH) pituitary islands or median eminence (ME)-stalk pituitary islands. The plasma corticosterone level was used as index of ACTH release. In rats with MBH pituitary islands, capsaicin failed to raise the plasma corticosterone level, but the intraperitoneal administration of E. coli endotoxin, histamine, insulin or a large subcutaneous dose of formaldehyde caused ACTH release which could not be distinguished from that in the controls. Histamine and insulin induced ACTH release even in rats with a ME-stalk pituitary island. It is suggested that E. coli endotoxin, histamine, insulin hypoglycaemia and large doses of formaldehyde may be classified as 'humoral' stimuli of ACTH release, since a neural afferent input to the MBH is not essential for their action. On the other hand, the integrity of some neural pathways to the MBH is essential for the ACTH-releasing effect of capsaicin.