k g / m 2 ) carried the 3 -Arg haplotype, compared with 11% of those who had a lower BMI (<31 kg/m 2 ), P = 0.02. Furthermore, BMI was ~2 kg/m 2 higher in Arg carriers compared with subjects who were Trp homozygous (P = 0.01) in the lower BMI group. No association of the 3 -Arg haplotype with metabolic parameters or blood pressure was found. F i n a l l y, the sensitivity for CGP12177 (a selective 3 - r e c e p t o r agonist) in visceral adipocytes was decreased 10-fold in 3 Arg compared with that in 3 - Trp subjects (P = 0.01). In conclusion, in this study, a well-conserved 3 -Arg haplotype is associated with moderate overweight and decreased receptor function. The 3 -adrenoceptor, which is mainly expressed in adipose tissue, is a candidate gene for the development of obesity and diabetes (2). Recently, a missense mutation in the coding region of the 3 -adrenoceptor gene was reported that results in the substitution of tryptophan to arginine at codon 64 (Trp64Arg) as reviewed (3). Subjects with the Arg variant had earlier onset of diabetes, increased capacity to gain weight, higher 2-h glucose levels, and higher waist-tohip ratios (WHRs) than did the wild-type subjects. However, several investigators have failed to demonstrate such relationships (4‐7). Furthermore, except for two studies performed in Japanese subjects (8,9), no reports have been able to present an increased frequency of the Arg variant in obesity. Moreover, neither in vitro (7) nor in vivo (10) studies have hitherto shown any significant consequence on adipocyte 3 -adrenoceptor function in subjects with the Trp to Arg substitution. Bearing in mind the reported opposing results on the importance of the Trp64Arg genetic variation, we examined the possibility that several different genetic variants in the 3 -adrenoceptor gene may exist in humans and that they also are functional. The study, which was approved by the Ethics Committee of Karolinska Institute, Stockholm, consisted of 211 nonrelated male or female Swedish subjects (both parents born in Scandinavia) who were either healthy volunteers not selected for body weight (n = 141) or otherwise healthy and drug-free subjects referred to the Department of Medicine because of uncomplicated obesity (n = 70). The subjects were between 19 and 70 years old and were investigated as outpatients. Obese subjects on recent antiobesity treatment or who were treated for diabetes, dyslipidemia, or hypertension were excluded. BMI (kilograms per meter squared) ranged from 18 to 38 kg/m 2 among volunteers and from 31 to 60 kg/m 2 in the subjects referred for obesity treatment. Maybe because of selection, the distribution of BMI was bimodal, with a clear cutoff point at 31 kg/m 2 . Subjects above this cutoff point were d e fined as belonging to the obese group, BMI = 40.9 ± 5.6 kg/m 2 (mean ± SD), and those below were defined as belonging to