Bacterial lipopolysaccharide (LPS, endotoxin) induces a dose-dependent release of TNF in whole human blood which has been diluted five-fold. It is modulated by interferon-gamma, prostaglandin E2 and indomethacin in the same manner as observed with tumour necrosis factor (TNF) release from human monocyte/macrophage cells cultured in vitro. The whole blood culture system (WBCS) can provide up to 250 samples from 10 ml of venous blood and enables an individual blood to be assessed in terms of TNF inducibility and its modulation by other biological agents. The whole blood culture system was used to demonstrate the individual variation between blood donors. The results demonstrated that the information provided by induced cytokine release and its regulation in the ex vivo system would be a valuable addition to that obtained from in vitro methods.