The ability of monophosphoryl lipid A (MPLA) to enhance nonspecific host resistance to bacterial infections was studied. Mice were treated with MPLA prior to intraperitoneal challenge with Escherichia coli or Staphylococcus epidermidis. Animals received additional MPLA for 2 days postinfection, and survival rates were determined. Ten micrograms of MPLA per mouse significantly improved the survival of animals infected with either bacterial species. Dose-response studies showed significant MPLA-induced protection at doses of 6 micrograms/kg against E. coli challenge and 60 micrograms/kg against S. epidermidis challenge.