The effect of serum from patients with cirrhosis and hepatocellular carcinoma on the release of prostaglandin E2 by the human histiocytic lymphoma cell line U937 was investigated to explain the mechanism underlying the immunoregulatory dysfunction of monocytes in cirrhosis and hepatocellular carcinoma. Prostaglandin E2 production by U937 cells cultured with serum from cirrhosis patients (5.9 ± 2.7 ng/ml, p < 0.01) and hepatocellular carcinoma patients (5.4 ± 2.6 ng/ml, p < 0.01) was significantly higher than that of control cultures (2.0 ± 1.0 ng/ml). This activity was decreased after heating and after freezing and thawing. By size exclusion fast protein liquid chromatography, the probable factor was eluted in the fraction with a molecular weight of 150 kD. By anion exchange chromatography with a stepwise increase of the NaCl concentration, the peak activity augmenting prostaglandin E2 production by U937 cells was eluted in the 0.05 to 0.1 mol/L NaCl fraction. The high level of this factor (monocyte-regulating factor) in patient serum might be one cause of abnormal monocyte immunoregulatory function in cirrhosis and hepatocellular carcinoma. (HEPATOLOGY 1991;14:1123–1128.)