Using an enzyme-linked immunosorbent assay, we measured plasma levels of tumor necrosis factor (TNF) in 38 patients who were treated with either antilipid A antibody or a placebo for presumed gram-negative bacteremia. Sixteen of the 38 patients had positive blood cultures: 14 with gram-negative rods and 2 with Streptococcus pneumoniae. Initial serum samples for TNF determinations were obtained within 2 to 72 hours (mean, 18.8 hours) after the onset of clinical signs of sepsis. Six (16%) of 38 patients had detectable TNF levels: 4 of 14 with positive blood cultures for gram-negative rods but only 2 of 22 with negative blood cultures (odds ratio, 4; 95% confidence limits, 0.5 and 24.3). Of the 6 patients, 4 had received the placebo and 2 had received the antibody. Tumor necrosis factor levels did not predict adult respiratory distress syndrome, shock, disseminated intravascular coagulation, renal failure, or mortality. The highest TNF levels (500 and 250 pg/mL) were observed in 2 patients with Enterobacter cloacae bacteremia who had received the placebo and antilipid A antibody, respectively. The other 2 patients with bacteremia and detectable TNF levels had positive blood cultures for Haemophilus influenzae (50 pg/mL) and Bacteroides fragilis (120 pg/mL), respectively. Despite negative blood cultures, the remaining 2 patients repeatedly had detectable TNF levels and a clinical picture consistent with gram-negative sepsis.