The effects of captopril, an angiotensin-converting enzyme inhibitor (ACEI), and a selective B2 kinin receptor antagonist (Icatibant) were examined on the paw edema and tissue contents of bradykinin (BK) and des[Arg9]BK following the intraplantar injection of carrageenan in rats. To this end, BK-like immunoreactivity (BK-LI) and des[Arg9]BK-LI were measured with highly sensitive and specific chemiluminescent enzyme immunoassays. Because pentobarbital significantly reduced the carrageenan-induced edema between 3 and 8 h, experiments were conducted in conscious rats. Icatibant (32.5 nmol/paw; intraplantar) significantly reduced carrageenan-induced paw edema between 3 and 8 h in captopril-untreated rats and at 1 and 3 h in captopril-treated rats (0.2 mg/kg x 5 days, per os). The paw content of BK-LI was increased 10-fold in captopril-untreated and 29-fold in captopril-treated rats 1 h after carrageenan injection. In parallel, des[Arg9]BK-LI was increased 8-fold in captopril-untreated and 24-fold in captopril-treated rats. Icatibant prevented the maximal increases in BK-LI and des[Arg9]BK-LI induced by carrageenan. It is concluded that inhibition of ACE by captopril enhanced the early production of endogenous BK and the edema formation induced by carrageenan through a B2 receptor-mediated mechanism. However, the B2 receptor does not appear to be involved in the late phase of the inflammatory response (from 5 to 24 h) to carrageenan in rats pretreated with ACEI. Although the concentrations of des[Arg9]BK were greater than those of BK, it is unlikely that B1 receptors play a significant role in this model of carrageenan-induced edema.