To investigate the pathogenesis of inflammatory bowel disease, it is critical to develop a system that uses simple and reproducible models for analyzing the "normal" mucosal defense mechanism. In the present study, germ-free mice were conventionalized by the oral administration of microorganisms prepared from the feces of genetically identical mice. Histological assessment and mucin characterization of small intestine and colon were then carried out. Histological findings in the gut were site-dependent and clearly time-dependent. Acute inflammation was most evident in the cecum. The cecal mucosa exhibited hyperplastic changes in epithelial cells, infiltration of polymorphonuclear cells, crypt abscesses, and epithelial projections on the epithelial surface 7 days after conventionalization. Some of the changes were similar to those seen in human ulcerative colitis. The histological findings in the conventionalized mice were comparable to those in specific pathogen-free mice after 28 days. Mucin histochemistry revealed that bacterial colonization altered the number of rectal goblet cells and the mucin composition in a time-dependent fashion. Although this model shares only some characteristics of human inflammatory bowel disease, it is unique in demonstrating the acquisition of mucosal defense. Understanding of this process is critical for the elucidation of inflammatory bowel disease pathogenesis.