A double-blind, randomized, placebo-controlled trial of 5% acyclovir ointment was carried out for thirty-one episodes of herpes labialis in thirteen patients experiencing severe, frequent recurrences. In addition, these patients continued to use acyclovir ointment or placebo for the treatment of twenty-two further episodes. Treatment was initiated by the patients as soon as possible after onset of prodromal symptoms, and continued five times a day for 5 days. It was found that acyclovir ointment shortened the duration of lesions only by about one day, but it greatly increased the number of abortive lesions resulting from early application. Acyclovir ointment is well tolerated and appears to modify the course of severe recurrent herpes labialis when therapy is initiated by the patient during the prodrome.