-Although widely assumed to have only satiating actions, nutrients in the gut can also condition increases in intake in some cases. Here we studied the time course of post-oral nutrient stimulation of ingestion in food-restricted C57BL/6J mice. In experiment 1, mice adapted to drink a 0.8% sucralose solution 1 h/day, rapidly increased their rate of licking (within 4 -6 min) when first tested with an 8% glucose solution and even more so in tests 2 and 3. Other mice decreased their licking rate when switched from sucralose to 8% fructose, a sugar that is sweet like glucose but lacks positive post-oral effects in mice. The glucose-stimulated drinking is due to the sugar's post-oral rather than taste properties, because sucralose is highly preferred to glucose and fructose in brief choice tests. A second experiment showed that the glucose-stimulated ingestion is associated with a conditioned flavor preference in both intact and capsaicin-treated mice. This indicates that the post-oral stimulatory action of glucose is not mediated by capsaicin-sensitive visceral afferents. In experiment 3, mice consumed flavored saccharin solutions as they self-infused water or glucose via an intragastric (IG) catheter. The glucose self-infusion stimulated ingestion within 13-15 min in test 1 and produced a conditioned increase in licking that was apparent in the initial minute of tests 2 and 3. Experiment 4 revealed that IG self-infusions of a fat emulsion also resulted in post-oral stimulation of licking in test 1 and conditioned increases in tests 2 and 3. These findings indicate that glucose and fat can generate stimulatory post-oral signals early in a feeding session that increase ongoing ingestion and condition increases in flavor acceptance and preference revealed in subsequent feeding sessions. The test procedures developed here can be used to investigate the peripheral and central processes involved in stimulation of intake by post-oral nutrients.conditioned flavor acceptance and preference; fructose; sucralose; capsaicin deafferentation; intragastric infusion THE OROSENSORY AND POST-ORAL nutritional properties of foods are important determinants of food intake and preference. The flavors of palatable foods, i.e., their taste, odor, and texture, stimulate feeding, whereas post-oral signals are often assumed to have only inhibitory action via satiation signals that terminate a feeding bout and satiety signals that suppress postmeal eating (10,24,56). However, there is extensive evidence that nutrients can have other post-oral effects that condition food preferences and, in some cases, increase intake (42). This has been demonstrated, for example, by studies in which rodents are trained to drink a flavored nonnutritive solution paired with intragastric (IG) self-infusion of a nutrient. Typically, animals are given multiple training trials with one flavor (the conditioned stimulus or CSϩ) paired with a concurrent IG nutrient self-infusion and a second flavor (CSϪ) paired with IG water self-infusion on alternate training days. T...