Ten immunosuppressed patients received intravenous adenine arabinoside (ara-A, 3.3-10 mg/kg per day for five to 13 days) for treatment of severe mucocutaneous infection due to Herpesvirus hominis (HVH). After ara-A, virus excretion by patients with orofacial lesions due to type 1 HVH infection was reduced 90% within 72 hr. By nine days, these lesions contained no virus and were healed, whereas three untreated patients had excreted -virus and had clinical lesions for two to 16 weeks. In contrast, type 2 HVH genitoperineal infection responded less well clinically and virologically. Nine neonates, six with disseminated HVH infection and three with localized HVH infection, were also treated with ara-A (10-15 mg/kg per day for five to 15 days). In contrast with the usually fatal outcome of disseminated HVH infection, three of the six neonates survived. The three with localized infection recovered without further extension of the disease. Unlike 5-iodo-2’-deoxyuridine and cytosine arabinoside, ara-A, within its apparent antiviral dose range, produced no demonstrable hepatic, renal, or hematologic toxicity. These preliminary data suggest a future role for ara-A in the treatment of severe HVH infections in man. © 1973 by the University of Chicago.