Glucose utilization studies show that sibutramine-induced thermogenesis is mediated via selective sympathetic activation of brown adipose tissue. The goal of the present study was to use a new calorimetry method in which resting metabolic rate is enhanced to evaluate the effects of sibutramine treatment on thermogenesis. Sixty obese women were included in the study. Subjects were divided into 2 equal groups-the placebo and sibutramine treatment groups. The sibutramine group was given sibutramine 10 mg daily for 12 wk. At baseline and at the end of the 12-wk treatment period, thermogenic measurements were taken with the use of water immersion calorimetry. Subjects were examined at weeks 4, 8, and 12 of treatment to identify adverse effects. Body mass index, measured at 31.5+/-2.05 kg/m2 in the placebo group, decreased to 30.4+/-2.94 kg/m(2) after 12 wk (P=.07). In the sibutramine group, it decreased from 33.5+/-4.1 kg/m(2) to 30.9+/-4.8 kg/m(2) (P<.05). In the sibutramine group, mean thermogenic response changed from a baseline value of 1.27+/-0.29 kcal/kg/h to 1.44+/-0.13 kcal/kg/h after 12 wk of treatment. In the placebo group, the baseline value was 1.56+/-0.27 kcal/kg/h; it changed to 1.33+/-0.36 kcal/kg/h at the end of 12 wk. The findings of this study suggest that sibutramine treatment promotes thermogenesis, thus facilitating weight loss. Calorimetry enhances resting metabolism through more efficient heat transfer from the body.