The contribution of intercellular adhesion molecule 1 (ICAM-1) during systemic and local bacterial infections was studied in transgenic ICAM-1-deficient and control mice that were injected intraperitoneally (ip) or intradermally (id) with Escherichia coli, Pseudomonas aeruginosa, or Staphylococcus aureus. Mortality rates, blood cultures, white blood cell (WBC) counts and absolute neutrophil counts (ANCs) were obtained daily until cultures were sterile. Six and 24 h after injections, autopsies were done on randomly selected ip-inoculated mice and biopsies were done on randomly selected id-inoculated mice. Survival rates were similar. In ICAM-1-deficient mice, ip P. aeruginosa resulted in higher incidences of bacteremia at 24 h (P = .003) and 48 h (P = .002); id S. aureus resulted in larger skin lesions (P = .026). Leukocytosis persisted in ICAM-1-deficient mice 6 h after ip injection of E. coli; however, WBC counts and ANCs in peritoneal fluid did not differ. Although the inflammatory responses were similar histologically in ICAM-1-deficient and normal mice, differences in site- and stimulus-specific susceptibilities were noted.