The results of experimental and clinical studies support the hypothesis that gut-derived endotoxins might be of relevance for the development and course of alcoholic liver disease. The aim of this study was to test the effect of a nonabsorbable, broad-spectrum antibiotic on endotoxemia in patients with alcoholic liver disease. Fifty patients with alcoholic liver disease (27 with cirrhosis, 23 without cirrhosis) were randomly assigned to receive either paromomycin sulfate (3 x 1 g/day) or placebo in a double-blind fashion for at least 3 weeks, and if possible 4 weeks. Endotoxin concentration, liver function tests, and other laboratory parameters were determined in weekly intervals. Endotoxin concentration was also determined in 15 healthy controls. Groups receiving paromomycin or placebo were similar for clinical and biological items collected initially. Mean initial endotoxin concentrations were significantly elevated in both groups (mean +/- SEM; paromomycin, 16.7 +/- 5.3 pg/ml; placebo, 17.5 +/- 6.9 pg/ml; healthy controls, 2.3 +/- 0.4 pg/ml). Although the mean endotoxin concentration was lower in the verum group after 1 week (paromomycin, 8.0 +/- 1.9 pg/ml; placebo, 14.6 +/- 3.5 pg/ml; p > 0.05), paromomycin treatment had no significant effect on endotoxin concentration or liver function tests during the 4-week period. The beneficial effect of paromomycin treatment on endotoxemia in cirrhotics reported in earlier studies could not be reproduced under the conditions of this trial in patients with alcoholic liver disease.