The cutaneous nociceptive response threshold to mechanical and thermal stimulation, the development of hyperalgesia and plasma extravasation after subcutaneous injection of carrageenan and the development of autotomy behaviour after nerve section were assessed in interleukin-6-deficient (IL-6-/-) and age-matched wild-type (IL-6+/+) mice. IL-6-/- mice had significantly lower response threshold to both mechanical and thermal stimulation in comparison to IL-6+/+ controls. Both IL-6-/- and IL-6+/+ mice developed hyperalgesia to mechanical and thermal stimulation after localized carrageenan injection, but the magnitude of the hyperalgesia was less in the IL-6-/- than in the IL-6+/+ controls. IL-6-/- mice also exhibited less plasma extravasation after carrageenan injection. No difference was noted between males and females in basal nociception and inflammatory hyperalgesia. However, female IL-6-/- mice exhibited autotomy behaviour, a sign of neuropathic pain, significantly more frequently and after a shorter interval following peripheral nerve injury than male IL-6-/- or male and female IL-6+/+ mice. It is suggested that IL-6-/- mice exhibited numerous changes in nociceptive responses compared to controls, some of which are sex related. The mechanisms of these changes in relation to null-mutation of the IL-6 gene and the influence of genetic background are discussed. 1997 Academic Press Limited.