The hepatobiliary histologic lesions of human newborns with biliary atresia have been compared to those induced in weanling mice by reovirus type III. Although the obliterative fibrotic lesions, the hallmark of human disease, are only transient or segmental in the mouse and therefore do not result in permanent or complete obstruction of bile flow, many of the inflammatory stages of the disease are identical in humans and in the mouse. Prompted by these similarities, antibodies to reovirus type III were sought in sera of human newborns with biliary atresia. Two of 12 babies had elevated and rising neutralizing titers to reovirus type III during the course of their illness. Using recobinant reoviruses which contain some genes from a nonpathogenic reovirus type I and other genes from the pathogenic parental reovirus type III, we have shown that hepatobiliary murine pathology is not the property of a single viral gene.