We used an experimental model of neurogenic inflammation, plasma extravasation induced by bradykinin or capsaicin, to study the effect of receptor-selective opioid agonists on plasma extravasation. Plasma extravasation was induced in the knee joint of the rat by continuous perfusion of either bradykinin (160 ng/ml), an inflammatory mediator produced at sites of tissue injury, that produces plasma extravasation significantly dependent on the sympathetic postganglionic neuron, or capsaicin (5 mg/ml), a C-fiber excitotoxin, that induces plasma extravasation that is dependent on both primary afferents and sympathetic post-ganglionic neurons. When selective delta-((d-Pen2,5)-enkephalin) or kappa-(trans-3,4-dichloro-N-methyl-N[2-(- pyrolidinyl)cyclohexyl]benzeneacetamide; U50,488H) opioid agonists were perfused with bradykinin, plasma extravasation was significantly attenuated. Co-perfusion of the non-selective opioid antagonist naloxone (1 microM), reversed this opioid-induced inhibition of bradykinin-induced plasma extravasation. In contrast, co-perfusion of a selective mu-opioid agonist (Tyr-d-Ala-Gly-NMe-Phe-Gly-ol) did not reduce bradykinin-induced plasma extravasation. Tyr-d-Ala-Gly-NMe-Phe-Gly-ol was, however, able to completely inhibit the plasma extravasation produced by capsaicin. These results suggest that delta- and kappa-, but not mu-selective opioids inhibit bradykinin-stimulated plasma extravasation, while a mu-selective opioid inhibits primary afferent-dependent plasma extravasation. Therefore, inhibition of neurogenic plasma extravasation by receptor-selective opioids may depend on the relative contribution to plasma extravasation of unmyelinated afferent and sympathetic postganglionic neuron terminals. Our findings can also explain, in part, the variation in anti-inflammatory effects of receptor-selective opioids reported in different inflammatory conditions.