We have investigated the ability of serotonin (5-HT) to induce an inflammatory reaction manifested as plasma extravasation and vasodilatation responses in a blister model in the rat hind footpad. The involvement of unmyelinated sensory fibres in these responses was investigated using capsaicin pretreated rats. 5-HT (0.1-10 microM), when perfused over the blister base, induced both plasma extravasation and vasodilatation responses in a dose-dependent manner. Both the plasma extravasation and the vasodilatation responses were maintained throughout a 30 min stimulation period. Neonatal capsaicin treatment resulted in a 78% and 56% reduction in the plasma extravasation and vasodilatation responses, respectively. The present results provide evidence for the involvement of capsaicin-sensitive sensory nerves in 5-HT-mediated plasma extravasation and vasodilatation responses in the rat.