SUMMARYThe modulating effect of captopril, an inhibitor of angiotensin‐converting enzyme, on the vascular permeability changes induced by intradermal injections of C5a, histamine and compound 48/80, was evaluated in guinea‐pigs. Cutaneous vascular permeability changes were measured by the extravasation of intravenously injected125I‐bovine serum albumin. Intraperitoneal injection of 12.5,25, or 50 mg/kg of captopril 30 min prior to the injection of C5a (10−11mol) significantly enhanced the increase in vascular permeability induced by this agent (P<0.02). This may be explained by the known property of captopril as an inhibitor of carboxypeptidase. No effect was observed when captopril was injected either 2 or 4 h before the injection of C5a. In contrast, the same doses of captopril, when injected intraperitoneally 2 h before the injection of histamine (10−8mol) or compound 48/80 (10 μg), significantly suppressed the increase in vascular permeability induced by these agents (P<0.02). This suppressive effect occurred in a captopril dose‐dependent manner. The ability of captopril to modulate the vascular permeability response induced by vasoactive agents indicates that it is a potentially useful tool to dissect the relative roles of mediators involved in inflammato