BACKGROUND Recently, missense mutation of the B3-adrenergic receptor gene has been shown to be associated with early onset of type 2 diabetes, abdominal obesity and an increased capacity to gain weight. This study was performed to investigate the effects of Trp64Arg mutation in the B3-adrenergic receptor gene on body fat distribution and weight loss in obese subjects. METHODS: Determination of the B3-adrenergic receptor gene mutation with restriction enzyme digestion method, anthropometry, various biochemical studies, including oral glucose tolerance test were performed in 99 obese and 35 control subjects. Body fat distributions were also evaluated by computerized tomography before and after weight-reduction program. RESULTS: I) There were no differences in the frequencies of Trp64Arg mutation in the B3-adrenergic receptor gene between obese and control subjects (15.2 vs 12.9 %). 2) The obese subjects with Trp64Arg mutation had higher waist to hip circumference ratio(WHR) (0.93 +/- 0.05 vs 0.87 +/- 0.04, p<0.001), visceral fat area (115.0 +/- 25.9 vs 86.4 +/- 41.4 cm, p=0.01), but decreased plasma free fatty acid (618.0 +/- 163.1 vs 817.5 +/- 248.2 pEq/L, p=0.001), and triglyceride level (118.7 +/- 36.2 vs 158.4 +/- 105.8 mg/dL, p=0.015) than those without mutation. 3) The obese subjects with Trp64Arg mutation had smaller decreases in weight (-3.4 vs -5.1 kg, p<0.001), body fat content (-2.1 vs -3.8 %, p<0.001), WHR (-0.01 vs -0.03, p=0.025), and abdominal fat masses (total, subcutaneous, and visceral fat) after weight-reduction program than those without mutation. CONCLUSION: Trp64Arg mutation in the B3-adrenergic receptor gene might be one of genetic loci contributing to central obesity and a predictor of difficulty in losing weight in obese subjects.