Context: The mechanisms underlying weight loss after Roux-en-Y gastric bypass (RYGBP) are not well understood. Objective: The objective of the study was to assess the changes in active glucagon-like peptide 1 (GLP-1) and total peptide YY (PYY) after RYGBP and examine their relationship with changes in hunger and satiety. Design:This was a prospective study on the changes in active GLP-1, PYY, hunger, and satiety in response to a standardized test meal in nine normal-glucose-tolerant obese subjects [body mass index (BMI) 47.4 6.1 kg/m 2 ] before and 6 wk after RYGBP. Results: Before surgery, meal ingestion failed to stimulate GLP-1 and PYY secretion. Six weeks after surgery, despite subjects still being markedly obese (BMI 43.6 7.8 kg/m 2 ), the area under the curve0‐120 of GLP-1 and of PYY in response to the standardized test mealweresignificantlyelevated(P0.05andP0.01,respectively). These hormonal responses were significantly larger (P 0.01) than those observed in a group matched for the BMI attained 6 wk after surgery.The2.91.2-and1.61.9-foldincrease,respectively,inthe area under the curve0‐120 of GLP-1 and PYY were accompanied by a significant decrease in fasting (P 0.05) and postprandial hunger (P 0.05) and a significant increase in satiety (P 0.05) after meal intake.Nevertheless,asignificantcorrelationbetweenchangesinthe hormonal and eating behavior parameters was not found. Conclusion: Our data show that RYGBP is associated with an improvement in the active GLP-1 and total PYY response to a liquidmeal intake. Moreover, we provide circumstantial evidence for a potential role of these gastrointestinal hormones on the decreased appetite after RYGBP. (J Clin Endocrinol Metab 91: 1735–1740, 2006)