Hyperglycemia may influence satiety. One mechanism by which glucose could influence food intake is hyperinsulinemia. Therefore, we investigated the short-term effects of acute hyperglycemia and euglycemic hyperinsulinemia on satiety. Six healthy volunteers (aged 20 to 26 years) were studied for 240 minutes on three separate occasions in random order during (1) intravenous (i.v.) saline (control), (2) acute hyperglycemic hyperinsulinemia (HG) with plasma glucose at 15 mmol/L, and (3) euglycemic hyperinsulinemia (HI) with plasma insulin at 80 mU/L and glucose at 4 to 5 mmol/L. Subjective criteria for appetite like the wish to eat, prospective feeding intentions ("How much food do you think you can eat?"), and feelings of hunger and fullness were scored on a 100-mm visual analog scale (VAS) at 30-minute intervals. Appetite was also measured every 60 minutes with the use of a food selection list (FSL). Appetite (prospective feeding intentions, feelings of hunger, and the wish to eat) gradually increased over basal levels during control conditions and HI. In contrast, prospective feeding intentions and feelings of hunger gradually decreased during HG and were significantly (P < .05) reduced versus basal and control levels during the last hour of the experiment. The wish to eat followed the same pattern. Feelings of fullness did not significantly change in all three experiments. Total food selection was not significantly decreased during HG, but the preference for fat-rich or carbohydrate-rich items tended to be reduced. The study suggests that in humans hyperglycemia induces satiety. This effect seems not to be mediated by insulin, since HI had no effect on appetite. However, a potentiating effect of endogenous insulin on the satiating effect of high blood glucose levels cannot be excluded.