Objective : We sought to elucidate further the mechanisms leading to weight loss after gastric bypass (GBP) surgery in morbidly obese individuals. Ghrelin is a gastroenteric appetite‐stimulating peptide hormone, fasting levels of which decrease with increasing adiposity and increase with diet‐induced weight loss. In addition, ghrelin levels rapidly decline postprandially. Research Methods and Procedures : We measured serum ghrelin responses to a 75‐g oral glucose tolerance test (OGTT) in 6 subjects who had undergone GBP surgery 1.5 ± 0.7 years before testing and compared these responses with 6 obese subjects about to undergo GBP surgery, 6 obese nonsurgical subjects (matched for BMI to the post‐GBP surgical group), and 5 lean subjects. Results : Despite weight loss induced by the GBP surgery, fasting serum ghrelin levels were significantly lower in the post‐GBP surgery group than in the lean subject (by 57%) or pre‐GBP surgery (by 45%) group. Serum ghrelin levels during the OGTT were significantly lower in postoperative than in lean, obese pre‐GBP surgical, or obese nonsurgical subjects. The magnitude of the decline in serum ghrelin levels between 0 and 120 minutes post‐OGTT was significantly smaller in postoperative (by 62%), obese pre‐GBP surgical (by 80%), or obese nonsurgical (by 69%) subjects in comparison with lean subjects. Discussion : Serum ghrelin levels in response to OGTT are lower in subjects post‐GBP surgery than in either lean or obese subjects. Tonically low serum ghrelin levels may be involved in the mechanisms inducing sustained weight loss after GBP surgery.