Neutrophil adherence to and emigration across endothelium are in large part dependent upon the neutrophil membrane CD11/CD18 glycoprotein complex. Recently, however, we have demonstrated that some stimuli can elicit neutrophil emigration in the lung by a CD18-independent pathway. We examined further the mechanism involved in CD18-independent emigration in a rabbit model of inflamed peritoneum. Neutrophil emigration in the peritoneum induced by instillation of E. coli and S. pneumoniae was studied under four experimental conditions: Group 1--normal peritoneum, Group 2--peritoneum primed with protease peptone to increase the number of macrophages, Group 3--peritoneum treated by protease peptone instillation and then depleted of the increased macrophage population, and Group 4--peritoneum with macrophages transplanted from animals enriched as in Group 2. Experiments were run in pairs with animals in each group assigned to receive either saline (control) or monoclonal antibody (MAb) 60.3 prior to bacterial instillation in the peritoneum. Neutrophil emigration in response to E. coli was greater than 86% inhibited by MAb 60.3 in both the normal and the macrophage-enriched peritoneum. Neutrophil emigration in response to S. pneumoniae was inhibited greater than 85% in the normal peritoneum and the macrophage-enriched and the transplanted macrophage peritoneum. These data indicate that macrophages can augment PMN emigration by a non-CD18 mechanism, and may explain the increased sensitivity of organs with large resident macrophage populations, liver and lung, to injury following shock and sepsis.