Intrathecal injection of 5-hydroxytryptamine (5-HT) in mice produced a behavioural syndrome consisting of reciprocal hindlimb scratching and biting or licking of the hindquarters. Pretreatment with either metergoline or morphine given intrathecally inhibited the 5-HT-induced behaviour. The response to 5-HT was similar to the effect of substance P (SP), and it was found that the blocker of the substance P receptor, D-Pro2, D-Trp7,9-SP, not only reduced the effect of substance P, but also that of 5-HT. The behaviour induced by substance P was also significantly reduced by intrathecal injection of either morphine or metergoline. These findings indicate a functional interaction between substance P and 5-HT in the modulation of sensory input at the spinal level.