Epidemiologic studies consistently report associations between obesity and dietary fat but not total energy intake. We measured ad libitum food intake in a laboratory setting and evaluated its relation to body weight and composition, energy expenditure, and macronutrient utilization in 28 women of Pima-Papago heritage (aged 27 +/- 7 y, 85.3 +/- 19.0 kg, 44 +/- 6% body fat; means +/- SD). All women were studied during the follicular phase of the menstrual cycle. After a 4-d weight-maintenance period, the volunteers selected their food for 5 d from computerized vending machines offering a variety of familiar and preferred foods, ie, a "cafeteria diet". Twenty-four-hour energy expenditure and substrate oxidation were measured in a respiratory chamber on the 4th d o weight maintenance and the 5th d of ad libitum intake. Average ad libitum intake was 13,732 +/- 4238 kJ/d (11 +/- 1% protein, 40 +/- 1% fat, 49 +/- 4% carbohydrate), ie, moderate overeating by 27 +/- 37% above weight maintenance requirements (range: -27% to 124%). Percent body fat correlated with daily energy intake (r = 0.53, P < 0.01), the degree of overeating (r = 0.41, P < 0.05), and the selection of a diet higher in fat and lower in carbohydrate (r = 0.70 and r = -0.63, respectively, P < 0.001). Excess carbohydrate intake caused an increase in carbohydrate oxidation (r = 0.51, P < 0.01), whereas excess fat intake resulted in a decrease in fat oxidation (r = -0.53, P < 0.01) and thus a positive fat balance of 85 +/- 65 g/d. The positive relations among degrees of obesity, dietary fat intake and overeating, and the fact that dietary fat does not induce fat oxidation, support the hypothesis that dietary fat promotes obesity in women.