Recent experiments have demonstrated that TNF plays an important role in the pathogenesis of septic shock. To confirm the involvement of TNF in human septic shock, serum TNF levels were measured in 10 adult patients admitted to the intensive care unit for sepsis with or without shock. Septic shock was corroborated by hemodynamic data (right catheterization, measurement of cardiac output by thermodilution). For TNF measurement, venous blood samples were withdrawn, as soon as possible after the onset of sepsis, into a pyrogen--free tube. Serum TNF levels were determined using a radioimmunoenzymatic assay (IRE Medgenix). During septic shock (n = 7), TNF levels were significantly higher (m = 354 +/- 131 pg/ml) than during sepsis without shock (n = 8; m = 145 +/- 35 pg/ml) (p less than 0.0005). TNF levels were also significantly higher in non-survivors (m = 392 +/- 111 pg/ml) than in survivors (m = 167 +/- 81 pg/ml) (p less than 0.0005). The value of 250 pg/ml seems to be critical: no patient without shock had TNF levels above 250 and all the patients who died early during the first 24 h) had TNF levels above 250. The TNF level is negatively correlated with the platelet count (r = -0.70; p less than 0.05). These data favor a pathophysiological for TNF in human sepsis and septic shock.