Eighteen 4-day-old gnotobiotic pigs were orally inoculated with porcine enteric calicivirus-like virus (C strain). Seven additional gnotobiotic pigs served as noninoculated controls. Mild diarrhea developed in all inoculated pigs by postinoculation day (PID) 3 and persisted for 3 to 7 days. Severe diarrhea developed in 2 inoculated pigs between PID 4 and 5. Twelve inoculated and 7 control pigs were euthanatized over a 7-day period. Small intestinal mucosal smears were stained with a fluorescein-conjugated anti-porcine enteric calicivirus-like virus serum. Immunofluorescence was observed in villous epithelial cells (primarily in the duodenum or jejunum) of all inoculated pigs, except for 1 pig euthanatized at PID 7. Villus length was determined in histologic sections of the small intestinal specimens from control and inoculated pigs. Statistically significant (P less than 0.01) villus atrophy was found in the duodenum and/or jejunum of inoculated pigs at PID 3 to 7. These observations were confirmed by scanning electron microscopy, which revealed shortening, blunting, fusion, or absence of villi in the duodenum and jejunum of inoculated pigs at PID 3 to 7. Lesions were not seen in control pigs. Calicivirus-like particles were detected by immune electron microscopy in the large intestinal contents and feces of inoculated pigs from PID 1 to 7.