The aim of this study was to determine whether the circadian rhythm of ornithine decarboxylase (ODC) activity in rat small intestine is controlled by factors other than luminal nutrients. ODC activity in duodenal and jejunal mucosa of rats fed ad libitum was measured at four time points (0500, 1100, 1700, 2300 h; light period: 0800-2000 h). ODC activity in the jejunum increased in the dark period, which is when rats normally eat. In contrast, ODC activity in the duodenum began to increase at 1700 h, which is when rats do not normally eat, as indicated by the recorded feeding pattern. The increase in ODC activity in the duodenum at 1700 h, but not at other time points, was abolished by subdiaphragmatic vagotomy, whereas vagotomy had no effect on the feeding pattern of rats. Subdiaphragmatic vagotomy had no effect on ODC activity in the jejunum. ODC activity in the duodenum increased following glycoprivation of the central nervous system induced by infusion of 2-deoxyglucose into the third cerebroventricle. These results indicate that the increase in duodenal ODC activity at 1700 h is due to a signal from the upper brain structure through the vagal nerve and not to luminal nutrient factors.