Dietary fibre consumption may help to control appetite and to reduce calorie intake. Underlying molecular mechanisms were not fully investigated. The aim of this study was to evaluate the effect of barley beta-glucans on short-term appetite and on satiety-related hormones in healthy subjects. Fourteen volunteers were selected and randomly assigned to have isocaloric breakfasts including a 3% beta-glucan-enriched bread (betaGB) or a control bread (CB). Post-breakfast individual self-records of appetite ratings and measure of calorie intake at an ad libitum lunch as well as measure of blood glucose, insulin, ghrelin and PYY concentrations, were performed. betaGB determined a significant higher reduction of hunger and increase of fullness and satiety than CB. Accordingly, a 19% reduction of energy intake at lunch subsequent to betaGB consumption compared to CB, was recorded. A 23% lower AUC(60-180) of plasma ghrelin and a 16% higher total AUC of PYY response after betaGB than CB consumption, independent from insulin response, was found. Glucose response was also blunted by betaGB vs CB. Barley beta-glucans were able to control appetite in the short term by modulating sensations and reducing energy intake. Data suggested for the first time that satiety effect of beta-glucans are mediated by ghrelin and PYY.