From 1975 to 1987, we had 56 patients of septic shock in the Department of Surgery. Multiple organ failure occurred in many septic patients. Glucocorticoids inhibited the secretion of chemical mediators (histamine, serotonin and bradykinin) and then prevented septic shock. Intravenous administration of dexamethasone showed no change in amounts of leukotrienes (LTC4, LTD4, LTE4) in venous blood in peritonitis rats. Dexamethasone treatment of septic rats corrected FDP and nearly normalized PEP values. When glucocorticoid was given intravenously at the time of cecal incision, PFKase, PKase, G6Pase and PEPCK were stimulated, respectively. Protease inhibitor FUT-175 was infused in 5% dextrose (0.1mg/ml/hr) in septic rats. Survival time was 12.1 +/- 2.3 hour in FUT-175 group and 6.6 +/- 1.1 hr without FUT-175. In FUT-175 injected rats G6P decreased by 20%, FDP increased 50% and lactate doubled. PEP levels increased 30% above peritonitis values. The amounts of leukotrienes (LTC4, LTD4, LTE4) in venous blood were gradually decreased by pretreatment with the specific 5-lipoxygenase inhibitor AA-861 after peritonitis. Specific treatments in septic shock should be instituted administration of glucocorticoid, antibiotics, protease inhibitor and lipoxygenase inhibitor. The importance of septic shock as a factor contributing to organ failure must be acknowledge. We believe that the prompt and efficacious treatment of septic shock is the best therapy.