Electrical stimulation of the trigeminal ganglion causes an increase in facial skin blood flow in the anaesthetised rat, as measured by laser Doppler flowmetry. We investigated the modulation of this neurogenic vasodilator response using selective receptor agonists for putative prejunctional inhibitory receptors, as well as other pharmacological agents to further characterise this response. [D-Ala2,Me-Phe4,Gly5-ol]enkephalin (DAGO, a mu-opioid receptor agonist) inhibited the vasodilator response in a dose-related (0.058-5.8 mumol/kg i.v.) and naloxone-sensitive manner. A similar inhibitory response was observed with the local anaesthetic lignocaine (2% w/v, s.c. 20 microliters). In contrast, the histamine H3-receptor agonist alpha-methylhistamine (15 or 35 mumol/kg, i.v.) and the 5-HT1D receptor agonists sumatriptan (0.24 or 2.4 mumol/kg, i.v.) and CP 122,288 (0.0003-3 mumol/kg, i.v.) had no effect on these responses. Similarly, atropine (1.5 mumol/kg, i.v.) and indomethacin (28 mumol/kg, i.v.) did not alter the vasodilatation observed in this model. In conclusion, only mu-opioid receptor activation and local anaesthetic had any inhibitory action on the neurogenic vasodilatation observed in this model.