Pretreatment with the novel neuropeptide nociceptin (20 micrograms kg-1, i.p.) caused an inhibition of plasma extravasation evoked by antidromic stimulation of the saphenous nerve or by topical application of 1% mustard oil on the skin of the acutely denervated hindleg of the rat. In contrast, it did not affect non-neurogenic inflammation evoked by s.c. injection of bradykinin after chronic denervation. Release of substance P (SP) and calcitonin gene-related peptide (CGRP) from rat isolated tracheae in response to electrical field stimulation was diminished by nociceptin (100 nM). It is concluded that nociceptin inhibits the release of sensory neuropeptides from terminals of nociceptive neurones.