Four fatal cases of neonatal herpes simplex infection occurred during a two-month period in the perinatal intensive care unit of a hospital. Virus isolation or serologic studies, or both, implicated herpesvirus hominis type 2 in all four cases. Three of the infants developed symptoms in the first week of life and were probably infected in utero or at delivery. The fourth infant did not develop signs of illness until age 6 weeks, an interval much longer than that expected with disease acquired at birth. An epidemiologic investigation indicated that the most likely source of this fourth infant's herpes infection was by indirect contact with one of the other three infected neonates. Nosocomial spread of herpes simplex virus within a hospital nursery, although uncommon, may pose an added risk to the newborn infant if nursery techniques among infants are compromised.