A double-blind, randomised trial of acyclovir versus placebo was conducted in 31 patients with initial and 85 patients with recurrent genital herpes. 17 patients with initial and 42 with recurrent disease were treated with 200 mg acyclovir by mouth five times a day for 5 days, and the remaining patients received matching placebo. In patients with initial genital herpes shedding virus acyclovir significantly reduced the duration of viral shedding, itching, and pain, the time to crusting and complete healing, and new lesion formation compared with controls. In patients with recurrence disease acyclovir significantly reduced the duration of viral shedding, time to complete healing, and new lesion formation. The reported incidence of adverse events was similar in both acyclovir and placebo groups. Oral acyclovir is effective and well tolerated in patients with initial and recurrent genital herpes and can be used in outpatient therapy.