1 The mechanisms involved in bradykinin (BK)-induced oedema in the rat paw as well as the interactions between BK and several inflammatory mediators, have been investigated. 2 Intraplantar injection of BK (1 nmol/paw) in rats pretreated with captopril (5 mg kg-', s.c.) caused a small amount of oedema formation (0.17 ± 0.05 ml). Des-Arg9-BK (DABK, a selective B, receptor agonist) up to 300 nmol/paw caused minimal oedema (0.03 ± 0.01 ml). 3 Co-administration of prostaglandin E2 (PGE2), prostaglandin 12 (PGI2), calcitonin gene-related peptide (CGRP), 5-hydroxytryptamine (5-HT), substance P (SP) or platelet activating factor (PAF) (1 pmol-1 nmol/paw) with BK (1 nmol/paw) dose-dependently potentiated BK-induced paw oedema.The rank order of potency (mean EDm, pmol/paw) for this effect was: SP (8.1)>PAF (13.7)>PGI2 (DALBK, up to 300 nmol/paw) had no effect. 5 Daily intraplantar injections of BK (10 nmol/paw) once a day for 7 consecutive days caused a progressive and complete desensitization of the paw oedema, which was specific for BK, since paw oedema induced by PAF, PGE2, SP or histamine was not affected. In addition, the oedema caused by BK in the paw desensitized to the peptide was almost completely reversed if BK was co-injected with PGE2, PGI2 or SP (1 nmol/paw). Injection of PGE2 or SP (10 nmol/paw) together with the first BK injection (1O nmol/paw), partially prevented BK-induced desensitization. 6 When animals were completely desensitized to BK, DABK (100nmol/paw) caused paw oedema (0.25 ± 0.03 ml) which was consistently blocked by the B, receptor antagonist, DALBK (100 nmol/ paw).7 Treatment of animals with dexamethasone (0.5 mg kg-', s.c., 24 h previously) antagonized paw oedema induced by DABK (100 nmol/paw) in desensitized paws, but not that induced by BK (3 nmol/ paw) in naive paws. The steroid also prevented the recovery of oedema seen after co-injection of BK with PGE2 or PGI2 (1 nmol/paw) in desensitized paws. 8 These results suggest that both B, and B2 receptors are involved in BK-induced rat paw oedema. The B2 receptors are constitutive, but induction of expression of B, receptors seems to occur only after complete desensitization of the paw to BK. In addition, very low doses of inflammatory mediators markedly potentiate BK-induced paw oedema and can attenuate BK-induced paw oedema desensitization. Such mechanisms may be relevant for the manifestation of acute and chronic inflammatory processes.