Rotavirus (RV) infections in newborns differ from those in older infants; the majority of RV infections that occur in neonates are mild or asymptomatic. Generally, fewer than one-third of RV-infected neonates have diarrhea, although rates have reached 77% in some hospital nursery populations. Cases with severe diarrhea, necrotizing enterocolitis, bowel perforation, and death have been reported, but such cases are very rare. Infection usually occurs during the first week of life and generally invokesa mucosal antibody response without a concomitant serologic anti-body response. Neonatal RV infections appear to incite an immune response that affords significant protection against severe RV-associated diarrhea, although not necessarily against a symptomatic RV infection later in life. Strains that cause neonatal infections differ from those that infect older infants; the outer-capsid protein VP4 is highly conserved in “nursery” RV strains, a property that probably plays a key role in their attenuated virulence. Immaturity of proteolytic enzymes in the neonatal gut and presence of secretory anti-RV IgA and trypsin inhibitors in breast milk are other factors that could account for the asymptomatic nature of RVinfections in newborns. Natural “nursery” strains of RV are currently being evaluated as vaccine candidates.