A controlled study was performed in 18 viral cirrhosis patients to evaluate whether immune function, as indicated by natural killer (NK) cell activity, was improved by a branched-chain amino acid-enriched nutrient mixture (nutrient-mixture), Aminoleban EN. Five patients received the nutrient-mixture (100 g/day) for 2 to 6 weeks preceded by control periods. Five additional patients received the nutrient-mixture for 2 to 4 weeks, and the remaining 8 patients did not receive the nutrient-mixture. NK cell activity, CD16, CD8, CD11b, and amino acids were assayed before and after the administration of the drug in the nutrient-mixture-supplemented group, and two times with 1 to 6 month intervals in the control group. In the nutrient-mixture-supplemented group (n = 10), increasing NK cell activity, expressed as the ratio of values of post-treatment to that of baseline (ratio > 1.25) was detected in 7 (70%) patients, whereas in the control group (n = 13), it was detected in only 1 (7.7%) (p < 0.01). While in the affected group (NK cell activity ratio > 1.25, n = 7), all patients had compensated liver cirrhosis, in the unaffected group (NK cell activity ratio < 1.25, n = 3), 2 of 3 patients had decompensated liver cirrhosis (p < 0.02). Laboratory data, indicating severity of liver cirrhosis, such as total bilirubin and albumin, showed better values (p < 0.01, p < 0.05 respectively), and baseline NK cell activity was low (8.7 +/- 7.2% vs 33.3 +/- 13.0%, p < 0.05) in the affected group than unaffected group. NK cell subpopulations such as CD16 (%), CD11b (%) and one of the populations of T cell such as CD8 (%) showed no significant change throughout the study. As for amino acids analysis, Fischer's ratio was increased in the nutrient-mixture-supplemented group compared to the control group (p < 0.05), but none of the amino acids showed significant change. Thus the changes in NK cell activity were not explained by increase in NK cell subpopulations nor changes of amino acids. These results suggest that the branched-chain amino acid-enriched nutrient mixture increases NK cell activity moderately in patients who have compensated liver cirrhosis and shows lower values of baseline NK cell activity.