This study was undertaken to investigate the requirement of β₂-integrins (CD11/CD18) for extravasation of neutrophils in mice. After intraperitoneal thioglycollate injection, an in vivo model of inflammation, leukocyte extravasation into the peritoneal cavity was studied in CD18-deficient and wild-type control mice. Before the induction of peritonitis, total and differential leukocyte counts in the circulation were analyzed and found to be 10-fold elevated in CD18-deficient animals compared with wild-type animals. This was largely due to neutrophilia, with a 30-fold increase in neutrophil counts. In CD18-deficient animals, extravasated white blood cells in the peritoneal cavity were diminished by 46%. The neutrophil number in the peritoneal fluid was severely reduced to 13% compared with control animals. In contrast, the number of emigrated monocytes was enhanced and lymphocyte emigration was not altered in the absence of CD18. The emigration efficiency of the neutrophils, calculated as ratio of the cell number in the lavage fluid and the circulating blood, was reduced to 0.4% in CD18-deficient mice compared with wild-type animals. Thus efficient neutrophil emigration into the peritoneal cavity strongly required CD11/CD18.