A randomised, double-blind, placebo-controlled cross-over study was conducted in 24 patients, nine females and 15 males, with a history of more than eight recurrences of genital herpes in the past year. The patients received a first treatment course with 400 mg acyclovir or matching placebo by mouth, twice daily, for 12 weeks. After cross-over patients received alternative medication for another 12 weeks. The patients were followed without treatment for a further three-month period. During acyclovir therapy, recurrences were completely prevented in 17 patients (71%) and the remaining seven patients had nine recurrences as compared to 18 recurrences while receiving placebo. The placebo treatment did not reduce the recurrence rate. No adverse effects were attributable to the acyclovir treatment period. All virus isolates tested after treatment remained sensitive to acyclovir. Acyclovir prophylaxis of recurrent genital herpes is effective and safe. A continuous suppressive therapy with acyclovir offers a basis for a normal sexual life to those patients severely incapacitated by their disease, but once medication is stopped, patients shed virus as before suppression.