To test whether glucose (GLC) or insulin (INS) acutely reduces spontaneous meal size, we tested the effects of remotely controlled, intrameal hepatic-portal vein infusions of GLC or INS on rats' spontaneous feeding patterns. Experiment 1 included four blocks of three test infusions and one control infusion. The test infusions in each block were 0.25, 0.5, 1.0 or 1.5 mmol GLC; 2, 4, 6, or 8 mU INS; or the four combinations with dose ratios of 1 mmol GLC/8 mU INS, respectively. Control infusions and the INS vehicle were saline infusions that were equiosmotic to the GLC infusion used in that block. Infusions (0.1 ml×5 min) were done during the first spontaneous dark-phase meal. None of the test infusions affected meal size, meal duration or the duration of the subsequent intermeal interval. In Experiment 2, a similar design was used to test infusions of 1 mmol GLC, 2 mU INS and GLC/INS. Both GLC alone and GLC/INS reduced the size and duration of the first spontaneous dark-phase meal. The subsequent intermeal interval was unaffected, but GLC alone also increased the satiety ratio (min/g) of the meal. The size and duration of the second dark-phase meal were unaffected. INS alone did not affect any meal parameters. In Experiment 3, infusions of 1 mmol GLC and 2 mU INS were repeated during each of the first three meals of the dark phase. These infusions reduced the size and duration of each meal, as well as 6-h cumulative food intake, but did not affect any other meal parameter. These experiments demonstrate for the first time that intrameal hepatic-portal infusions of GLC or of GLC and INS is sufficient to acutely and selectively reduce spontaneous meal size in the rat. The findings are consistent with the idea that meal-contingent changes in hepatic-portal GLC concentration contribute to satiation.