Long-term acyclovir therapy does not seem to reduce the rate of post-treatment herpetic recurrences. We report the results of long-term acyclovir followed by thymopentin, a synthetic polypeptide derived from the thymic hormone, for the treatment of highly recurrent genital and orofacial herpes simplex. We tried a 3-month regimen with acyclovir followed by 18 weeks of thymopentin in patients suffering from either orofacial or genital herpes. We obtained complete or partial responses with significant reduction in the recurrence rate in 88.9% of patients with orofacial herpes and in 84.6% of patients with genital herpes. We believe that the proposed treatment is of clinical value and is also to be recommended in terms of cost/benefit.