BACKGROUND Reports on the natural history of herpes zoster ophthalmicus stress its high morbidity related to vicious scars on eyelids, ocular complications, and post-herpetic neuralgia. Early treatment with oral acyclovir is effective, but the optimal duration of treatment has not been defined. METHODS The authors performed a bicentric, prospective, randomized, double-masked study of 86 patients with acute herpes zoster ophthalmicus, within 72 hours of skin eruption, who received oral acyclovir (800 mg 5 times daily), either for 7 days (plus 7 days oral placebo) or for 14 days. All patients concomitantly received ophthalmic 3% acyclovir ointment; follow-up was at least 6 months. RESULTS Statistical analyses of subjective symptoms, skin lesions, and ocular complications showed no significant differences between the groups, suggesting that a 7-day course of treatment was sufficient. Drug tolerance was good. Pooled data from both groups corroborated earlier reports that prompt treatment with oral acyclovir reduces the severity of the skin eruption, the incidence and severity of late ocular manifestations, and the intensity of postherpetic neuralgia. At 6 months, late ocular inflammatory complications were seen in 29.1% of our 86 patients, versus 50% to 71% of untreated patients described by others. Only 13% of our patients experienced post-herpetic neuralgia, which in no case required the use of analgesics. CONCLUSIONS The authors believe it is not useful to prolong treatment with 800 mg of oral acyclovir 5 times daily for more than 7 days in herpes zoster ophthalmicus. This study confirms the efficacy of oral acyclovir not only against skin lesions and ocular complications, but also against postherpetic neuralgia in herpes zoster ophthalmicus.