Intestinal lesions caused by a virus serologically unrelated to the calf diarrheal rotavirus or coronavirus were studied in gnotobiotic calves. The virion purified from feces from infected calves was a fringed particle with a diameter of about 100 nm. The incubation period from time of inoculation per orum to onset of diarrhea in calves was as short as 8 h. The viral infection in bacteria-free calves or calves not contaminated with pathogenic bacteria caused severe illness for only 24 h. When bacteria such as the K99 antigen Escherichia coli were present, the combined infection caused mortality. Lesions occurred only in the small intestinal villous epithelium. Calves euthanatized shortly before or after the onset of diarrhea had developed villous epithelial cell syncytia that contained numerous virions in the cytoplasm. Within 2-3 h after onset of diarrhea, the infected cells were shed and the villi had denuded tips or had cuboidal to squamous epithelial cells.