Sporadic diarrhea and weight loss were observed in a breeding colony of Syrian hamsters during a 2-year period. Thirteen adult hamsters with diarrhea, anorexia, and weight loss were examined. Histologic lesions consisted of diffuse nonsuppurative enterocecocolitis and multifocal epithelial proliferation in the cecum and colon. Goblet cell hyperplasia was extensive in the colonic mucosa of many hamsters. The hamsters in this colony had not been treated with antibiotics nor was Clostridium difficile isolated from any of the hamsters. In contrast to typical proliferative ileitis in hamsters, most hamsters involved in this outbreak were mature adults rather than weanlings, and lesions were predominantly inflammatory rather than proliferative and involved small intestine, cecum, and colon rather than ileum. The isolation of beta-hemolytic Escherichia coli and demonstration of Campylobacter-like organisms by transmission electron microscopy and Warthin-Starry staining suggest that these two agents were involved in the pathogenesis of this disease. Further studies, however, are needed to investigate the pathogenesis of this enteric syndrome in hamsters.