Stimulation of the saphenous nerve in the anaesthetised rat results in cutaneous neurogenic oedema formation. We have examined the effect of a tachykinin NK1 and a bradykinin B2 antagonist, and a mu-opioid agonist on plasma extravasation observed in response to two differing nerve stimulating parameters (10 V, 1 ms, 2 Hz and 25 V, 2 ms, 10 Hz). The NK1 antagonist SR140333 abolished oedema, supporting the theory that an NK1 agonist is a primary mediator of neurogenic oedema. The B2 antagonist HOE 140 had no effect, indicating a lack of involvement of B2 receptors in this response. The pre-junctionally acting mu-opioid agonist DAMGO significantly inhibited oedema formation at the 10 V, 1 ms, 2 Hz (P < 0.001), but not the 25 V, 2 ms, 10 Hz stimulation parameters. Thus a post-junctionally acting NK1 antagonist inhibited neurogenic oedema formation induced by both stimulation parameters, whilst a pre-junctionally acting mu-opioid agonist acted only at 10 V, 1 ms, 2 Hz parameters. These findings could be of interest with respect to therapeutic approaches of pathophysiological conditions which involve a neurogenic component.