BACKGROUND: Effects of protein intake on appetite-regulating hormones and their dynamics are unclear. OBJECTIVES: We investigated the satiating effects of meals with varying protein contents and whether there was an effect of dose on appetite-regulating hormones and appetite ratings.Design: Twenty-five men [mean ± SD age: 30.0 ± 8.7 y; body mass index (BMI; in kg/m(2)): 25.9 ± 4.7] participated in the 3-way, randomized, double-blind crossover study. Test meals were isocaloric with 30% of energy from fat and protein content adjusted at the expense of carbohydrate. Test meals were normal protein (NP; 14% of energy from protein), medium-high protein (MHP; 25% of energy from protein), and high protein (HP, 50% of energy from protein). Appetite ratings and blood samples were assessed every 0.5 h for 4 h. An ad libitum lunch was served 4 h after the meal. RESULTS: Protein increased dose-dependently glucagon-like peptide-1 (GLP-1), peptide YY (PYY) 3-36, and glucagon; MHP produced 10%, 7%, and 47% greater responses, respectively; and HP produced 20%, 14%, and 116% greater responses, respectively, than did NP (P <0.03). Compared with NP, HP increased insulin and cholecystokinin and decreased ghrelin and glucose-dependent insulinotropic polypeptide (P <0.05). Satiety and fullness dose-dependently increased by 7% and 6% for MHP and 16% and 19% for HP compared with NP (P <0.001). Hunger and prospective consumption dose-dependently decreased by 15% and 13% for MHP and by 25% and 26% for HP compared with NP (P <0.0003). There was a combined effect of GLP-1 and PYY 3-36 (P = 0.03) next to the additive effect of GLP-1 (P = 0.006) on the composite appetite score. No difference was shown in ad libitum energy intake. CONCLUSION: Protein dose-dependently increased satiety and GLP-1, PYY 3-36, and glucagon, which may, at least in part, be responsible for the satiety-stimulating effect of protein. This trial was registered at clinicaltrials.gov as NCT01561235.