Fatal viral infections in children with antibody deficiency syndromes are extremely rare. Two children with infantile X-linked hypogammaglobulinemia who died from overwhelming viral encephalitis are described. A 9-year-old boy developed encephalitis and both echovirus type 2 and herpes simplex virus were recovered from the brain at autopsy. The second patient was a 16½-month-old boy who developed encephalitis after receiving live measles virus vaccine and herpes simplex virus was recovered from the brain. Two viruses were involved in each case, but the relation is unknown. It is possible that cellular immunity was depressed by one virus, thus enhancing the severity of the infection by the second virus.