BACKGROUND:Observational studies have shown an inverse association between dietary calcium intake and body weight, and a causal relation is likely. However, the underlying mechanisms are not understood. OBJECTIVE: We examined whether high and low calcium intakes from mainly low-fat dairy products, in diets high or normal in protein content, have effects on 24-h energy expenditure (EE) and substrate oxidation, fecal energy and fat excretion, and concentrations of substrates and hormones involved in energy metabolism and appetite. DESIGN: In all, 10 subjects participated in a randomized crossover study of three isocaloric 1-week diets with: low calcium and normal protein (LC/NP: 500 mg calcium, 15% of energy (E%) from protein), high calcium and normal protein (HC/NP: 1800 mg calcium, 15E% protein), and high calcium and high protein (HC/HP: 1800 mg calcium, 23E% protein). RESULTS: The calcium intake had no effect on 24-h EE or fat oxidation, but fecal fat excretion increased B2.5-fold during the HC/NP diet compared with the LC/NP and the HC/HP diets (14.2 vs 6.0 and 5.9 g/day; Po0.05). The HC/NP diet also increased fecal energy excretion as compared with the LC/NP and the HC/HP diets (1045 vs 684 and 668 kJ/day; Po0.05). There were no effects on blood cholesterol, free fatty acids, triacylglycerol, insulin, leptin, or thyroid hormones. CONCLUSIONS: A short-term increase in dietary calcium intake, together with a normal protein intake, increased fecal fat and energy excretion by B350 kJ/day. This observation may contribute to explain why a high-calcium diet produces weight loss, and it suggests that an interaction with dietary protein level may be important.