Background/Aims: Fat feeding increases not only serum but also cerebrospinal fluid concentration of apolipoprotein (apo) A-IV, a protein produced mainly by the small intestine in the rat. We hypothesized that apo A-IV may have a central effect on gastric secretion. Methods: Gastric juice was collected by the pylorus ligation method. Rats underwent pylorus ligation and received intracistemal injection of apo A-IV under brief isoflurane anesthesia. Two hours after the injection, gastric juice was collected and gastric acid output determined. Results: Intracistemal injection of 0.5 μg apo A-IV had no effect on gastric secretion. However, gastric acid secretion was significantly inhibited by intracistemal injection of 1 ug apo A-IV. Furthermore, intracistemal administration of higher doses of apo A-IV (2.0 and 4.0 μg) resulted in greater inhibition of gastric acid secretion in a dose-dependent manner. On the contrary, 4 μg of apo A-I intracisternally injected failed to inhibit gastric acid secretion. Intraperitoneal administration of 15 μg of apo A-IV did not alter gastric secretion. Conclusions: These results suggest that apo A-IV may act in the brain to inhibit gastric acid secretion. Apo A-IV might be a central enterogastrone, which is a gastric inhibitor produced by the small intestine in response to fat feeding.