BACKGROUND: Decreased appetite and increased energy expenditure after oral consumption of red pepper has been shown. OBJECTIVE: The aim of the present study was to assess the relative oral and gastrointestinal contribution to capsaicin-induced satiety and its effects on food intake or macronutrient selection. METHODS: For 24 subjects (12 men and 12 women; age: 35+/-10 y; BMI: 25.0+/-2.4 kg/m2; range 20-30), 16 h food intake was assessed four times during 2 consecutive days by offering macronutrient-specific buffets and boxes with snacks, in our laboratory restaurant. At 30 min before each meal, 0.9 g red pepper (0.25% capsaicin; 80,000 Scoville Thermal Units) or a placebo was offered in either tomato juice or in two capsules that were swallowed with tomato juice. Hunger and satiety were recorded using Visual Analogue Scales. RESULTS: Average daily energy intake in the placebo condition was 11.5+/-1.0 MJ/d for the men and 9.4+/-0.8 MJ/d for the women. After capsaicin capsules, energy intake was 10.4+/-0.6 and 8.3+/-0.5 MJ/d (P<0.01); after capsaicin in tomato juice, it was 9.9+/-0.7 and 7.9+/-0.5 MJ/d, respectively (compared to placebo: P<0.001; compared to capsaicin in capsules: P<0.05). En % from carbohydrate/protein/fat (C/P/F): changed from 46+/-3/15+/-1/39+/-2 to 52+/-4/15+/-1/33+/-2 en% (P<0.01) in the men, and from 48+/-4/14+/-2/38+/-3 to 42+/-4/14+/-2/32+/-3 en% (P<0.01) in the women, in both capsaicin conditions. Satiety (area under the curve) increased from 689 to 757 mmh in the men and from 712 to 806 mmh in the women, both (P<0.01). Only in the oral exposure condition was the reduction in energy intake and the increase in satiety related to perceived spiciness. CONCLUSION: In the short term, both oral and gastrointestinal exposure to capsaicin increased satiety and reduced energy and fat intake; the stronger reduction with oral exposure suggests a sensory effect of capsaicin.