In Year 1 of this two-year trial, patients with six or more genital herpes recurrences in the past year received suppressive treatment with either acyclovir, 400 mg, or placebo, orally twice daily for one year, and physician-documented recurrences were treated with open-labeled acyclovir, 200 mg, orally five times per day for five days (acute treatment). In Year 2, patients received open-labeled acyclovir treatment either with daily suppressive therapy or intermittent acute therapy. Among 683 patients who completed two years of treatment, 348 received continuous suppressive treatment for two years, 276 received acute treatment in Year 1 and suppressive treatment in Year 2, 24 received suppressive treatment in Year 1 and acute treatment in Year 2, and 35 received acute treatment for two years. Patient groups receiving intermittent acute acyclovir treatment experienced means of 7.0 to 12.6 recurrences/year during treatment as compared with 1.4 to 1.9 recurrences/year among groups receiving continuous suppressive treatment. No patients who received acute treatment remained recurrence-free for two years as compared with 29 percent of patients receiving continuous acyclovir suppression for two years. There was no evidence of cumulative toxicity detected by clinical, hematologic, or blood chemistry evaluations performed monthly in Year 1 and quarterly in Year 2. Suppressive oral acyclovir therapy remained effective and well-tolerated in this two-year trial.