The objective of this study was to analyze monokine production by peripheral blood mononuclear cells from patients with alcoholic cirrhosis. The capacity of peripheral blood mononuclear cells and purified monocytes from these patients to produce tumor necrosis factor a, interleukin 18, and interleukin 6 was investigated. Spontaneous production of tumor necrosis factor a, interleukin 6 and interleukin 18 was similar in cirrhotic and healthy subjects, but serum levels of interleukin 6 (<2 U/ml vs. 9.6 f 3 U/ml) and tumor necrosis factor a (3.1 2 1.2 pg/ml vs. 12.0 & 1 . 2 pglml) were significantly higher in cirrhotic patients. However, peripheral blood mononuclear cells or purified monocytes from patients with alcoholic liver cirrhosis, stimulated in uitro with Escherichiu coli lipopolysaccharide, displayed a marked increase of tumor necrosis factor a, interleukin l p and interleukin 6 secretions compared with healthy controls. A striking feature of this overproduction was its reversibility as assessed by allowing cells to rest in uitro without lipopolysaccharide for 1 to 7 days before stimulation. In such conditions, tumor necrosis factor a and interleukin 6 secretions declined to levels present in healthy subjects in whom production remained stable, whereas interleukin 1s secretion markedly decreased in both groups to the point where no difference could be seen. This reversible oversecretion of cytokines after lipopolysaccharide stimulation, along with the lack of abnormality of spontaneous cytokine secretion, suggests that monocytes in these patients may have undergone an in viuo activation process analogous to a priming phenomenon. The in oifro activation with lipopolysaccharide may represent the correlate of in uiuo endotoxemia observed during acute events such as sepsis. This might leadpossibly through the recognized cytopathic and cytotoxic effects of excessive production of monokinesto the decompensation of the underlying liver disease. Monokine oversecretion