This study provides significant new evidence substantiating a role of the postganglionic sympathetic neuron in plasma extravasation in the knee-joint of the rat. Increased plasma extravasation produced by the potent inflammatory mediator bradykinin was mimicked by 6-hydroxydopamine, a selective stimulator of sympathetic fibers. Various treatments (chemical sympathectomy, co-perfusion with the local anesthetic lidocaine, or co-perfusion with depolarizing concentrations of potassium) similarly modulated plasma extravasation induced by both bradykinin and 6-hydroxydopamine, but not that produced by platelet activating factor. We also showed that bradykinin is able to release norepinephrine in the knee-joint, indicating action on the sympathetic postganglionic neuron. In summary, these experiments provide substantial additional evidence supporting a significant contribution of the sympathetic post-ganglionic neuron terminal to inflammatory plasma extravasation.