Granulocyte-macrophage colony-stimulating factor (GM-CSF) potentiates in vitro and in vivo production of granulocytes. Also, recombinant human GM-CSF in vitro enhances functional capabilities of human granulocytes. Recombinant murine (rm) GM-CSF was administered to neonatal rats in vivo to test its ability to protect from septic death due to Staphylococcus aureus. When rmGM-CSF was given intraperitoneally 6 h beforea 90% lethal dose challenge of S. aureus, peak survival was observed at a dose of 30 pg/g (54% vs. 10% in animals administered saline; P < .001). Blood cultures were positive for S. aureus in 26 of 32 saline-treated and in 5 of 31 rmGM-CSF-treated animals (P < .001). Numbers of blood granulocytes were significantly increased 9 h after administration of rmGM-CSF (30 pg/g) but returned to control levels by 12 h. Neither neutrophil storage nor proliferative pools were affected. Thus, rmGM-CSF significantly improved survival when given prophylactically in a neonatal rat model of infection.