We previously demonstrated epithelial induction of serum amyloid A in germ-free mice inoculated with luminal bacteria. The aims of the present study were to investigate the role of luminal bacteria and mucosal inflammation in epithelial expression of this acute-phase protein using germ-free and dextran sulfate sodium-treated mice in vivo and HT29 cells in vitro. Immunoreactivity for serum amyloid A was detected in the epithelium of esophagus, stomach, duodenum and rectum regardless of the presence or absence of luminal bacteria. Administration of dextran sulfate sodium resulted in colonic epithelial induction of serum amyloid A at the mRNA and protein levels in parallel with the progression of mucosal inflammation. Epithelial induction of serum amyloid A is possibly relevant to mucosal inflammation because that was observed in bacteria-reconstituted and dextran sulfate sodium-induced colitis in vivo and because interleukin-beta and lipopolysaccharide induced its mRNA in vitro.