We have recently reported that obese women randomized to a low-carbohydrate diet lost more than twice as much weight as those following a low-fat diet over 6 months. The difference in weight loss was not explained by differences in energy intake because women on the two diets reported similar daily energy consumption. We hypothesized that chronic ingestion of a low-carbohydrate diet increases energy expenditure relative to a low-fat diet and that this accounts for the differential weight loss. To study this question, 50 healthy, moderately obese (body mass index, 33.2 +/- 0.28 kg/m(2)) women were randomized to 4 months of an ad libitum low-carbohydrate diet or an energy-restricted, low-fat diet. Resting energy expenditure (REE) was measured by indirect calorimetry at baseline, 2 months, and 4 months. Physical activity was estimated by pedometers. The thermic effect of food (TEF) in response to low-fat and low-carbohydrate breakfasts was assessed over 5 h in a subset of subjects. Forty women completed the trial. The low-carbohydrate group lost more weight (9.79 +/- 0.71 vs. 6.14 +/- 0.91 kg; P < 0.05) and more body fat (6.20 +/- 0.67 vs. 3.23 +/- 0.67 kg; P < 0.05) than the low-fat group. There were no differences in energy intake between the diet groups as reported on 3-d food records at the conclusion of the study (1422 +/- 73 vs. 1530 +/- 102 kcal; 5954 +/- 306 vs. 6406 +/- 427 kJ). Mean REE in the two groups was comparable at baseline, decreased with weight loss, and did not differ at 2 or 4 months. The low-fat meal caused a greater 5-h increase in TEF than did the low-carbohydrate meal (53 +/- 9 vs. 31 +/- 5 kcal; 222 +/- 38 vs. 130 +/- 21 kJ; P = 0.017). Estimates of physical activity were stable in the dieters during the study and did not differ between groups. These results confirm that short-term weight loss is greater in obese women on a low-carbohydrate diet than in those on a low-fat diet even when reported food intake is similar. The differential weight loss is not explained by differences in REE, TEF, or physical activity and likely reflects underreporting of food consumption by the low-fat dieters.