A murine model of peritonitis was used to test the role of platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) in acute inflammation. A monoclonal antibody (mAb) specific for murine PECAM-1 injected intravenously 4 h before the intraperitoneal injection of thioglycollate broth blocked leukocyte emigration into the peritoneal cavity for up to 48 h. This block was particularly evident for neutrophils. Control mAb, including one that bound to murine CD18 without blocking its function, failed to block emigration when used at the same or higher concentrations. The decreased emigration seen with the anti-PECAM-1 antibody was not due to neutropenia or neutrophil sequestration in the lung, spleen, or other organs; peripheral blood leukocyte counts were not diminished in these mice. In the mesenteric venules of the mice treated with anti-PECAM-1 mAb, leukocytes were frequently seen in association with the luminal surface of the vessel, but did not appear to emigrate. Thus, the requirement for PECAM-1 in the transendothelial migration of leukocytes previously seen in an in vitro model holds true in this in vivo model of acute inflammation.