The risk of serious bacterial infection (SBI) in febrile infants who are classified as low risk (LR) or high risk (HR) by the Rochester criteria has been established. LR infants average a 1.4 percent occurrence of SBI, whereas HR infants have an occurrence of 21 percent. The occurrence of SBI in Rochester LR or HR infants with confirmed viral infections is unknown. The objective of this study was to determine the occurrence of SBI in Rochester LR and HR infants with and without viral infections. All febrile infants who were 90 days or younger and evaluated at Primary Children's Medical Center (Salt Lake City, Utah) between December 1996 and June 2002 were eligible. Infants were classified as Rochester LR or HR, and discharge diagnoses were collected. Viral testing for enteroviruses, respiratory viruses, rotavirus, and herpes virus was performed. Of 1,779 infants enrolled, 78 percent had some form of viral diagnostic testing and 35 percent had one or more viruses identified. By the Rochester criteria, 33 percent of infants were classified as LR and 67 percent of infants as HR. For infants with viral infections, the occurrence of SBI was significantly lower than in infants without a viral infection. Rochester HR virus-positive infants had significantly fewer bacterial infections than HR virus-negative infants. The study concluded that febrile infants with confirmed viral infections are at lower risk for SBI than those in whom a viral infection is not identified. Viral diagnostic data can positively contribute to the management of febrile infants, especially those who are classified as high risk.