The effects of the tachykinin antagonist Spantide II (D-Nic-Lys1,3-Pal3,D-Cl2Phe5,Asn6,D-Trp7,9,Nl e11)-substance P (SP) and the vasoactive intestinal peptide (VIP) antagonist (Ac-Tyr1,D-Phe2)-GRF(1-29)-NH2 on the excitability of the spinal nociceptive flexor reflex to intrathecally (i.t.) applied SP and VIP, respectively, as well as the facilitation evoked by activation of cutaneous C-afferent was examined. Both antagonists blocked the effects of the respective neuropeptides in rats with both intact and sectioned sciatic nerves. Spantide II antagonised C-afferent induced reflex facilitation in rats with intact nerves, but the degree of antagonism declined after axotomy. In contrast, the VIP antagonist did not block C-afferent induced facilitation in rats with intact nerves, but did so after axotomy. The results indicate that the role of tachykinins in mediating C-afferent-induced reflex facilitation is taken over by VIP after axotomy.