An open controlled trial of ursodeoxycholic acid (UDCA) for chronic non-A, non-B hepatitis was performed using randomized envelope method. Twenty-five patients were treated with UDCA for twelve weeks at two different doses: low dose (n = 13, 150 mg/day; approximately 2.5 mg/kg body weight) and high dose (n = 12, 600 mg/day; approximately 10 mg/kg body weight). Anti-HCV (anti-C 100-3) was positive in 77% (10/13) in low dose group and in 67% (8/12) in high dose group. AST, ALT, gamma-GPT and total bilirubin were significantly improved both in low dose and high dose groups. Although the improvement in these indices seemed to be more sustained and apparent in high dose group, the degree of improvement did not differ in the two groups and no dose-dependence was observed. Serum total bile acid concentration did not change significantly in both groups (low dose group: 9.3 plus or minus 1.8 to 8.9 plus or minus 2.1 micromol/l, high dose group: 14.4 plus or minus 4.6 to 36.7 plus or minus 15.5 micromol/l). UDCA represented 35.0 mol% of total bile acid in low dose group and 44.6% in high dose group (p = 0.06). Amelioration of anorexia or dyspepsia was seen in 31% (4/13) in low dose group and 25% (3/12) in high dose group. No adverse reaction related to UDCA was observed throughout the course. These results suggest that UDCA may be safe and effective treatment for chronic non-A, non-B hepatitis. While the two doses did not significantly differ in its effects, larger study is needed to elucidate appropriate dose of UDCA for the treatment of chronic hepatitis.