Bradykinin (10–6 and 10–5M) stimulated ACTH-IR release from rat anterior pituitary tissue in vitro concentration-dependently. The onset of this effect was delayed in comparison to that of AVP or CRF. The combined treatment of bradykinin with AVP or CRF produced additive effects of ACTH-IR release. Bradykinin may represent another candidate involved in the regulation of ACTH release. In contrast to AVP, bradykinin did not stimulate prostaglandin E2 synthesis in the pituitary tissue. Bradykinin-induced ACTH-IR release remained unchanged following cyclooxygenase inhibition by indomethacin. It can be concluded that prostaglandins are not involved in the action of bradykinin on the anterior pituitary. Bradykinin did stimulate cyclic AMP accumulation in pituitary tissue. Inhibition of phosphodiesterase by 3-isobutyl-1-methylxanthine (IBMX) potentiated the ACTH-IR release evoked by bradykinin. From the results obtained, we concluded that cyclic AMP appears to be involved as a second messenger in the bradykinin-evoked ACTH-IR rele