This study set out to examine the vasomotor effects of the opioid-like peptide nociceptin on knee joint capsular blood flow using urethane anaesthetised rats. Topical application of nociceptin (10^-15 - 10^-8 mol) caused a progressive fall in joint perfusion which was significantly inhibited by the specific nociceptin receptor antagonist [Phe¹-(CH₂-NH)-Gly²] Nociceptin(1-13)-NH₂ as well as the non-specific opioid antagonist naloxone. To test whether this constrictor response was sympathetically mediated, nociceptin was administered in animals treated with either guanethidine to produce sympathetic blockade, or in the presence of the -adrenoceptor antagonist phentolamine. Both guanethidine treatment and phentolamine co-administration attenuated the constrictor response to nociceptin. Inhibition of nociceptin-mediated vasoconstriction revealed a supplementary hyperaemic response which persisted in animals whose knee joints were treated with 1% capsaicin to destroy the articular unmyelinated nerve supply. These results show that in the rat knee, peripheral administration of nociceptin primarily causes a sympathetically-mediated vasoconstriction. In addition, high dose nociceptin produces a vasodilatatory response which is likely due to the direct action of nociceptin on vascular smooth muscle and not by a neurogenic mechanism.