Gross, light microscopic, and morphometric changes were observed in the small intestines of 11 neonatal gnotobiotic dogs after oral inoculation with a canine rotavirus. Starting in pups killed at postinoculation hour (PIH) 24, gross changes consisted of moderate dilatation and thinning of the walls of the small intestine, hyperemia, and a moderate amount of semiliquid-to-liquid greenish-yellow intestinal contents. In the jejunum and ileum of inoculated pups killed from PIH 18 to 48, columnar villus epithelial cells on the upper one-third of the villus were necrotic, and foci denude of epithelium were seen on the upper regions of villi. Inoculated pups killed from PIH 24 to 72 had mild-to-moderate villus atrophy in the jejunum and ileum, villi covered with cuboidal-to-flat squamous-like epithelial cells, and absence of large, clear vacuoles in the jejunal and ileal villus epithelial cells similar to those seen in villus epithelial cells of 9 control pups. Microscopic sections of the jejunum and ileum from inoculated pups killed from PIH 72 to 154 showed slight-to-moderate villus atrophy, and the villi were covered with cuboidal-to-low columnar epithelial cells. Morphometric results indicated lower mean villus-crypt ratios in the duodenum, jejunum, and ileum of inoculated pups. In addition, the morphometry of the small intestine indicated that crypt cell hyperplasia occurred in the duodenum early during infection without obvious villus atrophy, and hyperplasia of the crypt cells in the jejunum and ileum was observed later during the infection.