Strategies of treatment of chronic hepatitis type B are currently based on the use of either antiviral or immunomodulatory agents. A randomized, controlled trial was performed to assess the safety and efficacy of 6-month thymopentin therapy in 30 patients with chronic hepatitis B. Inclusion criteria were biopsy-proven chronic hepatitis, elevated alanine aminotransferase and serum HBsAg and HBV-DNA positivity for at least 12 months. At the conclusion of the study (1 year), HBV-DNA was negative and alanine aminotransferase had normalized in 13% and 20% of treated cases and in 20% and 27% of controls. None of the ten treated and one of the nine control patients who were initially HBeAg positive subsequently cleared HBeAg. None became HBsAg negative. A histologic improvement was noted in 27% of the treated patients compared with 18% of controls. These results indicate that this regimen of thymopentin therapy is not effective in treating chronic hepatitis B.