In Japan, glycyrrhizin therapy is widely used for chronic hepatitis C and reportedly reduces the progression of liver disease to hepatocellular carcinoma. The aims of this study were to evaluate the effect of glycyrrhizin on serum alanine aminotransferase (ALT), hepatitis C virus (HCV)-RNA and its safety in European patients. Fifty-seven patients with chronic hepatitis C, non-responders or unlikely to respond (genotype 1/cirrhosis) to interferon therapy, were randomized to one of the four dose groups: 240, 160 or 80 mg glycyrrhizin or placebo (0 mg glycyrrhizin). Medication was administered intravenously thrice weekly for 4 weeks; follow up also lasted for 4 weeks. Within 2 days of start of therapy, serum ALT had dropped 15% below baseline in the three dosage groups (P 0.1). No major side-effects were noted. None of the patients withdrew from the study because of intolerance. Glycyrrhizin up to 240 mg, thrice weekly, lowers serum ALT during treatment, but has no effect on HCV-RNA levels. The drug appears to be safe and is well tolerated. In view of the reported long-term effect of glycyrrhizin, further controlled investigation of the Japanese mode of administration (six times weekly) for induction appears of interest.