A newborn infant whose condition was diagnosed as herpes simplex encephalitis and who had subsequent recurrences of skin disease had repeated episodes of neutropenia while receiving therapy with intravenous (30 mg/[kg.d]) or oral (30 mg/]kg.d]) acyclovir. The neutropenia did not recur when the dosage of oral acyclovir was reduced to 10 mg/(kg.d). This case represents the first well-documented report of acyclovir-induced neutropenia.