A randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy and safety of thymosin alpha 1 (alpha 1) in treating chronic hepatitis C. Nineteen Italian patients with chronic active hepatitis C, proven by biopsy were randomly assigned to receive a six month course of thymosin alpha 1 (900 micrograms/m2 of body surface area twice weekly) or a placebo. All had HCV-RNA in their serum (by PCR), with serum ALT levels more than double the upper limit of the normal range for at least six months before enrollment. After treatment, patients were followed for an additional six months. All patients completed the trial. One patient treated with thymosin alpha 1, but no patient in the placebo group, normalized serum ALT levels by the end of the treatment. This patient, however, relapsed at the sixth month of the follow up. Overall, there were no significant changes in mean serum ALT levels in either group during the treatment or follow-up period. No patient cleared HCV-RNA. No side effects were reported except for local discomfort at the injection sites, reported by some patients treated with thymosin alpha 1. In conclusion, this regimen of thymosin alpha 1 is not effective in the treatment of chronic hepatitis C.