A double-blind, placebo-controlled study was undertaken to evaluate the long-term efficacy and safety of oral acyclovir suppressive therapy over a 1-year period. Results from the multicenter trials, based on a total of 261 patients with frequently recurring genital herpes, were analyzed. Of the patients enrolled in the study, 131 received oral acyclovir capsules (800 mg) daily and 130 received placebo capsules. Medication was taken twice daily. Analysis of data from patients who completed a full year of therapy demonstrated that only 5% of patients receiving placebo were free from recurrences, as compared with 46% of acyclovir recipients. The mean number of recurrences for patients on acyclovir therapy was 1.8, as compared with a rate of 8.7 recurrences for the placebo group over the course of the year. The mean time to the first recurrent herpes outbreaks was 19 days for the placebo group and 274 days for the acyclovir-treated patients. There were no significant differences between the two groups in laboratory data or in the frequency or nature of side effects reported. Daily administration of acyclovir capsules for 1 year is a safe and effective therapy for control of frequent recurrences of genital herpes.