This study was designed to determine the effect of steroid/antibiotic treatment on the survival of baboons subjected to LD100 Escherichia coli shock. Fourteen baboons (Papio c. cynocephalus), randomly divided into three groups, were anesthetized and administered 2-hr infusions of LD100 viable E. coli. Group A received E. coli alone; Group B was administered E. coli followed by infusions of both gentamicin sulfate (GS) (18 mg/kg) and methylprednisolone sodium succinate (MPSS) (75 mg/kg) during a 12-hr period. Group C was given E. coli plus GS (18 mg/kg) alone. Groups B and C baboons were also given GS intramuscularly, 4.5 mg/kg at 12 hr and twice daily for 3 days. Insensible fluid loss during the intial 12-hr period was replaced by minimal volumes of saline. Fully treated baboons (Group B) received steroid after 0.7 × 1010 organisms/kg body wt had been administered. All fully treated baboons survived; however, all animals of Groups A and C died within 42 hr. Systemic hypotension observed in every baboon within 2 hr was reversed in Group B animals. Hypoglycemia, hypoinsulinemia, anuria, and extensive adrenal pathology were prevented by steroid/antibiotic treatment. Serum creatinine and blood urea nitrogen concentrations increased in all baboons but returned to normal in the fully treated group. Increased survival may have been due in part to augmented antibacterial activity elicited by (a) improved peripheral distribution of the antibiotic and (b) stimulation of the bone marrow by the steroid. Findings demonstrate that the lethal pathophysiology of E. coli-induced shock is effectively prevented by combined steroid and antibiotic therapy.