Experiments were designed to investigate the role of kinin B(1) and B(2) receptors in Freund's adjuvant (CFA)-induced inflammation and nociception responses by the use of B(1) and B(2) null mutant mice. Intradermal (i.d.) injection of CFA produced time-dependent and marked hyperalgesic responses in both ipsilateral and contralateral paws of wild-type mice. Gene disruption of the kinin B(2) receptor did not interfere with CFA-induced hyperalgesia, but ablation of the gene of the B(1) receptor reduced the hyperalgesia in both ipsilateral (48+/-13%, at 12 h) and contralateral (91+/-22%, at 12 h) paws. Treatment of wild-type mice with the selective B(1) antagonist des-Arg(9)-[Leu(8)]-BK (150 nmol/kg, s.c.) reduced CFA-evoked thermal hyperalgesia, to an extent which was similar to that observed in mice lacking kinin B(1) receptor. I.d. injection of CFA produced a time-related and long-lasting (up to 72 h) increase in paw volume in wild-type mice. A similar effect was observed in B(1) knockout mice. In mice lacking B(2) receptor, the earlier stage of the CFA-induced paw oedema (6 h) was significantly greater compared with the wild-type animals, an effect which was almost completely reversed (76+/-5%) by des-Arg(9)-[Leu(8)]-BK. This data demonstrates that kinin B(1) receptor, but not B(2) receptor, exerts a critical role in controlling the persistent inflammatory hyperalgesia induced by CFA in mice, while B(2) receptor appears to have only a minor role in the amplification of the earlier stage of CFA-induced paw oedema formation. The results of the present study, taken together with those of previous studies, suggest that B(1) receptor antagonists represent a potential target for the development of new drugs to treat persistent inflammatory pain.