We evaluated, in a randomized double-blind trial, the efficacy of oral paromomycin sulfate administration in the prevention of endotoxemia in 24 cirrhotic patients with endotoxemia. Renal function was evaluated by glomerular-filtration rate and renal plasma flow at the beginning and at the end of the study period. After the administration of paromomycin sulfate, 2 g/day for 4 weeks, endotoxemia disappeared in 10 out of 13 (76.9%) cirrhotic patients with endotoxemia, whereas it became negative in only 3 of the 11 (27.3%) treated with placebo, the difference being significant (P less than 0.05). With regard to correlation of endotoxemia with renal impairment, endogenous creatinine clearance and p-aminohippurate clearance were significantly improved (P less than 0.02) in those patients whose endotoxemia disappeared on paromomycin sulfate administration. We did not find significant improvement, however, neither in liver function or in blood coagulation tests in the same patients. Paromomycin sulfate seems to be effective in the prevention of endotoxemia and the associated renal impairment in cirrhosis in man.