In order to assess the role of tumor necrosis factor (TNF) in neonatal sepsis, plasma TNF levels were determined by a method using L929 cells at the time of septic work-up in 67 neonates. Thirty-three patients with sepsis were found to have significantly higher TNF levels (533.33 +/- 468.74 U/ml; 1 U corresponding to 1.67 pg recombinant TNF) as compared with 34 non-sepsis patients (100.0 +/- 188.97 U/ml) and 30 healthy newborns (27.33 +/- 16.17 U/ml, P < 0.05, respectively). The upper limit of normal plasma TNF levels was 60 U/ml and the best cutoff value for predicting neonatal sepsis was 160 U/ml. This had remarkable sensitivity (88%), specificity (82%), positive predictive value (83%), and negative predictive value (88%). Plasma TNF levels were significantly associated with the occurrence of shock, organ failure, scleroma and outcome. Thus, anti-TNF antibodies might be used in protecting newborns from septic death.