In a randomized, double-blind, multicenter trial we compared the efficacy of a preparation of human IgG antibody to Escherichia coli J5 (J5-IVIG) with that of a standard IgG preparation (IVIG) for the treatment of gram-negative septic shock. At study entry, patients received a single intravenous dose of 200 mg/kg of body weight (maximal dose, 12 g) of either J5-IVIG or IVIG. Of the 100 patients randomized, 71 (30 receiving J5-IVIG and 41 receiving IVIG) had a documented gram-negative infection. Mortality from gram-negative septic shock was 50% (15 of 30) in J5-IVIG recipients and 49% (20 of 41) in IVIG recipients. In addition, treatment with J5-IVIG did not reduce the number of systemic complications of shock and did not delay the occurrence of death due to septic shock. Thus we conclude that J5-IVIG was not superior to IVIG in reducing mortality or in reversing gram-negative septic shock.