Apolipoproteins play a central role in transport and metabolism of lipids in animals. We investigated the regulatory mechanisms responsible for expression of apolipoproteins in the small intestine. Animal experiments using surgical procedures suggested that the biliary component is a luminal factor regulating apolipoprotein A-IV expression in the intestine. In addition, peptide YY stimulated the apolipoprotein A-IV expression in Caco-2 intestinal cells in a dose- and time-dependent manner, suggesting that peptide YY is a humoral factor regulating the expression of apolipoprotein A-IV. Furthermore, intravenous infusion of hexamethonium and atropine, but not propranolol, diminished apolipoprotein A-IV mRNA levels in the rat ileum, suggesting the presence of basal cholinergic stimulatory expression of the apolipoprotein A-IV gene in the ileum. In conclusion, we propose that expression of apolipoprotein A-IV in the intestine is regulated by luminal, humoral, and neural factors. We also discuss the relationship between the hypocholesterolemic action of dietary beet fiber and hepatic expression of the apolipoprotein A-I gene in rats.