We assayed serial plasma samples from 86 patients, who were enrolled in a prospective randomized trial of the effects of methylprednisolone (MPSS) in septic shock, for the presence of cytokine tumor necrosis factor (TNF) using an enzyme-linked immunosorbent assay. TNF was present in the plasma of 27 of the 74 patients with septic shock, but in only 1 of the 12 patients with shock due to other causes. TNF was detected with equal frequency in patients with shock from gram-negative or from gram-positive bacillary sepsis. TNF levels were highest on the initial sample and decreased significantly over the subsequent 24 h in both the patients treated with MPSS and in those given placebo. Patients with detectable TNF had a higher incidence and severity of the adult respiratory distress syndrome and a higher mortality rate than did patients without detectable TNF.