Objective: To evaluate the effectiveness of a polyclonal immunoglobulin (Ig) preparation containing IgG, IgM, and IgA as an adjunctive therapy for septic shock. Design: Prospective, randomized clinical trial. Setting: A clinical immunology ward at the center for internal medicine in a university hospital. Patients: Fifty-five patients with septic shock were randomly allocated to two groups according to criteria of septic shock. Intervention: One group of patients (n = 27) received a commercially available immunoglobulin preparation (containing high titers of antibodies specific for determinants to bacterial endotoxin) during the first 3 days after inclusion in the study. The other randomized group (n = 28) did not receive any immunoglobulin preparation. Measurements and Main Results: During the period of less-than-or-equal-to 6 wks after the beginning of clinically apparent septic shock, death related to the septic process occurred in one (4%) of 27 patients who received immunoglobulin. By comparison, nine (32%) of 28 control group patients died during this period (p < .01). Within the first 48 hrs after onset of the clinically apparent septic process, significantly increased activity of circulating endotoxin and simultaneously decreased specific IgG serum titers to lipid A were detected in the group of nonsurvivors. Conclusions: Administration of a polyclonal immunoglobulin preparation in the early phase of septic shock was associated with significantly improved survival.