Addition of capsaicin (CAPS) to the diet has been shown to increase satiety; therefore, CAPS is of interest for anti-obesity therapy. We investigated the effects of CAPS on appetite profile and ad libitum energy intake in relation to energy balance. Fifteen subjects (seven women and eight men, age: 29.7 +/- 10.8yrs, BMI: 23.3 +/- 2.9 kg/m2) underwent four conditions in a randomized crossover design in 36 hour sessions in a respiration chamber; they received 100% of their daily energy requirements in the conditions "100%Control" and "100%CAPS", and 75% of their daily energy requirements in the conditions "75%Control" and "75%CAPS", followed by an ad libitum dinner. In the 100%CAPS and 75%CAPS conditions, CAPS was given at a dose of 2.56 mg (1.03 g of red chili pepper, 39,050 Scoville heat units) with every meal. Satiety (P < 0.05) and fullness (P = 0.01) were measured every waking hour and before and after every meal using visual analogue scales, and were higher in the 100%CAPS versus 100%Control condition. After dinner desire to eat, satiety and fullness did not differ between 75%CAPS and 100%Control, while desire to eat was higher (P < 0.05) and satiety (P = 0.06) and fullness (P = 0.06) tended to be lower in the 75%Control versus 100%Control condition. Furthermore, ad libitum intake (P = 0.07) and overconsumption (P = 0.06) tended to decrease in 100%CAPS versus 100%Control. In energy balance, addition of capsaicin to the diet increases satiety and fullness, and tends to prevent overeating when food intake is ad libitum. After dinner, capsaicin prevents the effects of the negative energy balance on desire to eat.