BACKGROUND: Hepatitis C is an important cause of chronic liver disease. It is claimed that Complete Thymic Formula, an over-the-counter herbal dietary supplement, is beneficial for patients with hepatitis C. OBJECTIVE: To evaluate the efficacy and safety of Complete Thymic Formula. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Tertiary referral center. PATIENTS: 38 patients with hepatitis C who did not respond to or were intolerant of interferon therapy. INTERVENTION: Complete Thymic Formula for 3 to 6 months or placebo for 3 months. MEASUREMENTS: Serial measurements of hepatitis C virus (HCV) RNA titers. RESULTS: No differences were noted at 3 months between the placebo group (n = 13) and the treatment group (n = 19) in mean HCV RNA titers (4.06 +/- 1.52 x 10(6) copies/mL compared with 3.48 +/- 1.92 x 10(6) copies/mL; P > 0.2). The 19 patients who completed 6 months of treatment with Complete Thymic Formula remained positive for HCV, and their mean HCV RNA titers were similar at 6 months and at baseline (2.78 +/- 1.96 x 10(6) copies/mL compared with 3.12 +/- 1.94 x 10(6) copies/mL; P > 0.2). CONCLUSIONS: Complete Thymic Formula did not benefit patients who had previously received interferon therapy. Patients should be advised about use of this over-the-counter compound.