Piglets infected with transmissible gastroenteritis virus, compared to matched-fed littermates, had massive diarrhea characterized by increased quantities and concentrations of sodium, potassium, and chloride. Determinations of Na-K-ATPase in mucosal homogenates from small and large intestine revealed decreased activity of this enzyme in the upper small bowel. Our data indicate that a defect in active sodium transport in this region may be an important factor in the pathogenesis of the diarrhea. Further studies using this model should help to define the mechanisms producing diarrhea in acute infantile gastroenteritis.