During the summer of 1968 ECHO virus type 31 was isolated from four infants in a neonatal intensive care unit. The index case was admitted from home in a comatose state and harbored ECHO 31 in his throat. Necropsy findings were inconclusive, and no virus was recovered from neural tissues. After the admission of this patient, two infants in the unit developed apneic spells and ECHO 31 was isolated from their CSF, throat, and stool samples. The virus was also isolated from the stool of an asymptomatic infant. ECHO 31 had not been recovered in newborn infants prior to its isolation in these cases. The isolation techniques currently used in many neonatal units may be inadequate to prevent viral dissemination. It is important to maintain a high index of suspicion of neonatal viral disease since careful virologic study will clarify the ecology of these nosocomial infections.