CONTEXT: Obesity prevalence is generally higher in women than in men, and a paucity of research with sex-specific approaches exists. The question arises whether current weight loss programmes, largely developed and tested on women, are appropriate for men. OBJECTIVE: Investigate 24 h energy metabolism, satiety and related hormones during a diet relatively high in protein (HP), exchanged with carbohydrate compared to an adequate-protein (AP) diet, in a respiration chamber in men, in comparison with previous outcomes in women. DESIGN: Ten healthy males (BMI: 22.5+/-1.6 kg/m(2), age: 25+/-3.5 y) were fed in energy balance with an AP (10/60/30% of energy of protein/carbohydrate/fat) or a HP (30/40/30% of energy of protein/carbohydrate/fat) diet in a randomized cross-over design. RESULTS: During the HP diet, 24 h Energy Expenditure (10.5+/-0.5 versus 10.0+/-0.5 MJ/d; p<0.05), Sleeping Energy Expenditure (7.1+/-0.3 vs 6.9+/-0.2 MJ/d;p<0.05), protein balance (0.5+/-0.02 vs 0.0+/-0.01 MJ/d;p<0.05), satiety (AUC) p<0.05, and plasma GLP-1 concentrations (42+/-23 versus 28+/-16 AUC; p<0.005) were significantly higher and 24 hRQ (0.80 vs 0.85;p<0.01), fat balance (-0.85+/-0.03 vs 0.05 vs 0.03 MJ/d;p<0.01) and hunger (AUC) p<0.05, were significantly lower. Comparisons reveal a stronger reaction in men in energy expenditure and substrate oxidation, whereas satiety reacted stronger in the women. CONCLUSIONS: Effects of a diet relatively high in protein exchanged with carbohydrate, versus an adequate protein diet are a stronger increased energy expenditure, fat oxidation, protein anabolism in men, and a stronger increased satiety in women, thereby creating sex-specific conditions for long-term use for body-weight management.