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Four gnotobiotic calves were inoculated intranasally with Breda virus within two hours after cesarean section. Three calves developed diarrhea between 48 and 60 hours after inoculation; one calf was killed at 36 hours. Consistent microscopic findings in the intestinal mucosae of calves with diarrhea were cytopathologic changes in enterocytes of the lower small intestine, large intestine, and dome epithelial cells and an acute inflammatory response with cellular infiltration and subtle changes in capillaries. Virions with average dimensions of 35 x 80 nm were seen in rounded cells that had severe cell swelling, dilatation of the cytocavitary network, and hydropic degeneration. Virions were most often in multiple, large autophagolysosomes. There was a good correlation in detection of virus in cells with electron microscopy and indirect immunofluorescence. No lesions were detectable in two control calves killed five days after inoculation.