Objectives: Interleukin-10 (IL-10) has been implicated in immune deficiency in patients with cancer. The relationship of this cytokine as measured in serum to anti-tumor immunity and prognosis was investigated in unresectable hepatocellular carcinoma. Methods: This study consisted of 74 consecutive patients with unresectable hepatocellular carcinoma (median age, 65 years). Forty-four healthy age-matched subjects and 32 patients with cirrhosis but no carcinoma served as controls. Patients with hepatocellular carcinoma were divided into those with serum IL-10 concentrations above (high group, n = 39) or below (low group, n = 35) 10 pg/ml. Results: Age, gender, Child-Pugh grade, and tumor stage distributions were similar in high and low groups. The patients of high group showed lower in lymphokine-activated killer (LAK) and natural killer (NK) activities than those of low group (P < 0.01 and 0.01, respectively). Serum IL-10 concentration was a significant factor contributing to low activities of LAK and NK by logistic regression analysis (P < 0.05 and 0.05, respectively). The high group had a significantly shorter survival (median, 3 months) than low group (median, 12 months; P < 0.02, generalized Wilcoxon test). Conclusions: These data suggest that serum IL-10 concentration is a possible factor contributing to poor prognosis and low anti-tumor immunity in patients with unresectable hepatocellular carcinoma. (C) 2003 Elsevier B.V. All rights reserved.