Serum levels of TNF-alpha were evaluated in 29 patients with sepsis, using TNF-alpha sensitive L929 cells (sensitivity = 15 pg/ml). Blood samples were collected serially at the first 24-36 h of symptoms. Seventeen patients had severe underlying disease and 12 patients had mild or no underlying disease. Shock was present in 25 patients. Overall mortality was 62.1%. TNF-alpha was detected in nine patients (range: 57.7-3,169 pg/ml). There was a tendency to detect TNF-alpha in patients with mild or no underlying disease (p = 0.07). Detection of TNF-alpha was associated with survival (p = 0.0003) even when adjusted for severity of underlying disease (p = 0.005), shock (p = 0.0005), coagulation abnormality (p = 0.002) and immunosuppressive therapy (p = 0.005), using a bivariate analysis. In this investigation, detection of circulating TNF-alpha was predictive of good outcome in septic patients, suggesting a role for this cytokine in host-defense against this kind of infection.