Vibrio mimicus, a causative agent of gastroenteritis, has also been reported to attribute to extraintestinal infections. Recently we have purified a metalloprotease produced by the pathogen: however, the role of the protease in V. mimicus infection has not been documented. The V. mimicus protease (VMP) was found to enhance vascular permeability and form edema when injected into the dorsal skin of guinea pig and rat. The permeability enhancement by VMP was observed in a dose-dependent manner in both guinea pig and rat skin. In guinea pig, an inhibitor of the angiotensin-converting enzyme was found to augment the permeability enhancement reaction. The permeability enhancement was significantly blocked by soybean trypsin inhibitor (SBTI), an inhibitor of plasma kallikrein reaction. In vitro conversion of plasma prekallikrein to kallikrein by VMP was also noted. In rat skin, the permeability enhancement reaction was not blocked by antihistamine or SBTI. However, the reaction was partially blocked when a mixture of antihistamine and SBTI was administered with VMP. It is apparent from the study that in guinea pig skin, VMP enhances vascular permeability through activation of plasma kallikrein-kinin system which generates bradykinin, whereas in addition to the activation of plasma kallikrein-kinin cascade in the case of rat, stimulation of histamine release from mast cells and other unknown mechanism seem to be also a cause of the permeability enhancement reaction. These results suggest that VMP may play a role in extraintestinal infections with edema caused by the pathogen.