Twenty-three infants less than six weeks of age with fever of 100.4 degrees F, or higher and no evidence of bacterial infection were seen at the Cincinnati General Hospital from July to December, 1971. Seventeen of these were admitted to the hospital; 15 were treated with penicillin and kanamycin for possible sepsis. Viral isolation was attempted on 21 of these infants, and ECHO viruses were isolated from 14 (66.7 per cent), compared to three (14.3 per cent) of 21 controls. Eleven of the 14 ECHO viruses isolated were type 4, and the other 3 were types 6, 11, and 25 respectively. Acute and convalescent serum was obtained from 11 of the 21 infants; seven had a fourfold rise in antibody to ECHO virus type 4. Most of the children had fever with irritability, six of the 23 had a fine maculopapular rash, and three had aseptic meningitis. This study suggests that ECHO viruses may be a significant cause of febrile illness in young infants during the summer and fall and may account for illnesses which lead to hospitalization as possible sepsis.