Between July 18 and August 5, 1986, a cluster of echovirus 11 infections occurred in hospitalized neonates. Ten infants were affected and one died. All cases occurring after the index case were infants who were in the nursery for at least 1 day when the index patient was also present. Risk factors for secondary infection included low birth weight or gestational age and receipt of antibiotics, red blood cell transfusions, nasogastric intubation or gavage feedings. Because viral infection had not been suspected in the index patient, isolation measures were not instituted until after onset of secondary cases. We conclude that more severely ill infants receiving intensive levels of care are at increased risk for nosocomial enteroviral infection. These infants may have a greater likelihood of exposure to the virus and/or increased host susceptibility. Outbreaks caused by cross-infection may be preventable by early recognition of patients colonized or infected with potentially pathogenic agents and prompt institution of appropriate isolation measures.