It has been suggested that the asymptomatic nature of most rotavirus infections that occur in newborn nurseries is a result of the low virulence of strains that are readily transmitted and persist in the nursery without calling attention to their presence or without requiring intervention to interrupt transmission. The high degree of sequence relatedness between the fourth gene of the M37 strain (derived from an asymptomatic newborn in Venezuela) and other strains recovered from asymptomatic neonatal infections in other locations suggested that this gene was related to the putative low virulence of the neonatal strains. Furthermore, the gene 4 of neonatal strains differs significantly in sequence from that of strains with similar VP7 serotype specificity isolated from older infants with diarrhea. To extend these observations, we obtained additional nursery specimens from various locations as well as strains recovered from older infants with diarrhea and examined them by hybridization and sequencing techniques. The results indicate that: (i) the M37 gene 4 allele is associated with long-term persistent rotavirus transmission in newborn nurseries that is not associated with significant diarrheal disease, (ii) other strains sharing their gene 4 with wild type rotaviruses associated with diarrhea in older infants may be found in asymptomatic neonates, but these strains have not been associated with persistence and silent transmission of rotavirus in newborn nurseries, and (iii) strains with a M37-like gene 4 may cause diarrhea in older infants, but this is an infrequent event.