In previous studies we showed that granulocyte colony-stimulating factor (G-CSF) improved and neutrophil CD18-directed monoclonal antibodies (MAb) worsened endotoxemia, cardiovascular function, and survival in lethal Escherichia coli peritonitis in canines. To better understand the contrasting effects of these two agents, we have now studied G-CSF and CD18 MAb either alone or in combination in endotoxin-challenged canines. These studies have shown that treatment with G-CSF directly stimulates endotoxin clearance and improves cardiovascular function via CD18-independent mechanisms and that CD18 MAbs worsen cardiovascular function without altering serum endotoxin levels. This study in combination with our previous work in bacteria- challenged canines emphasizes the importance of neutrophil-mediated host defense against microbial toxins as well as microbes themselves. These studies suggest that therapies designed to inhibit neutrophil integrin function during disease potentially complicated by infection may be detrimental. They also suggest that stimulating neutrophil function with agents such as G-CSF might be beneficial in some patients at risk of infection.