Over 25 episodes of severe chronic and recurrent mucocutaneous herpes simplex virus infections in five immunodeficient patients were successfully treated with intravenous or oral acyclovir treatment. Acyclovir was shown to inhibit viral shedding rapidly, to be well tolerated, and to permit the complete healing of lesions. As expected, a course of acyclovir did not prevent later recurrences of the herpes virus infections. However, symptomatic recurrences were successfully suppressed during long (up to 65-day) courses of oral acyclovir.