Among 13 neonates with herpes simplex virus (HSV) infection, eight had disseminated disease, one localized CNS disease, and in four the infection was confined to the skin and eyes. Ara A, a purine nucleoside with anti viral activity against DNA viruses, was given (10 to 20 mg/kg/day) by a continuous 12 hour intravenous drip for 10 to 15 days. In all, ara A administration was begun within 3 to 8 days after the appearance of skin vesicles which represented the hallmark of the disease. Both diagnosis and ara A treatment were much delayed in one infant without skin vesicles and 4 infants whose skin vesicles appeared late, long after the occurrence of CNS damage. In this group of infants with disseminated disease, four died and one infant was left with severe neurological deficits. Eight infants (4 with disseminated and 4 with localized skin disease) with skin vesicles as the earliest sign of infection received ara A early, within three days after the onset of neurologic signs. All survived with no neurologic deficit at 6 months to 1 year of age. There was no apparent toxicity of ara A to the bone marrow, liver, or kidney.