Increasing the protein content of a diet results in increased satiety and energy expenditure (EE). It is not clear whether the magnitude of these effects differs between proteins differing in concentrations of indispensable amino acids (IAA). We hypothesized that a protein lacking IAA may stimulate appetite suppression and EE and may limit positive protein balance. Therefore, we compared appetite, EE, and substrate balances between gelatin (incomplete protein) and casein (complete protein) in single-protein diets with either 25 or 10% of energy (En%) from protein. During a 36-h stay in a respiration chamber, 23 healthy men (n = 11) and women (n = 12) (BMI, 22.2 +/- 2.3 kg/m(2); age, 25 +/- 7 y) consumed 4 isoenergetic diets: 25 En% (25/20/55 En% protein/fat/carbohydrate) and 10 En% (10/35/55 En% protein/fat/carbohydrate) casein or gelatin diet in a randomized crossover design. For 3 d before the study, participants consumed a diet at home with similar macronutrient distribution as the diet they would receive during the subsequent stay in the chamber. Hunger was suppressed 44% more (P < 0.05) and protein balance was more negative when consuming the 10 En% gelatin diet (-0.17 +/- 0.03 MJ/d) compared with the 10 En% casein diet (-0.07 +/- 0.03 MJ/d; P < 0.05); carbohydrate and fat balances did not differ between the treatments. EE did not differ when participants consumed the 25 En% or 10 En% diets. Participants were in higher protein balance (0.56 +/- 0.05 vs. 0.30 +/- 0.04 MJ/d; P < 0.0001), lower carbohydrate balance (0.86 +/- 0.14 vs. 1.37 +/- 0.17 MJ/d; P < 0.01), and similar negative fat balance when they consumed the 25 En% casein compared with the 25 En% gelatin diet. In conclusion, when we compared the effects of an incomplete protein (gelatin) and a complete protein (casein) at 2 concentrations over 36 h, gelatin resulted in a greater appetite suppression; casein caused a greater positive (smaller negative) protein balance, and effects on EE did not differ. In terms of weight loss for people with obesity, the greater hunger-suppressing effect of gelatin may play a role in reducing energy intake if this effect is maintained when consuming a gelatin diet in the long term. In addition, long-term use of casein may contribute to preservation of fat-free mass.