Since recent data suggest that the endocannabinoid system controls food intake through central, and lipogenesis via peripheral CB1 receptors, we hypothesized that genetic variation at the cannabinoid receptor-1 (CNR1) locus could have an effect on adiposity. We investigated, whether a specific CNR1 G1422A genotype is associated with anthropometric markers of obesity and fat distribution in adult obese individuals. A total of 1,064 obese subjects (BMI > or = 30 kg/m2) without diabetes, impaired glucose tolerance or other endocrine diseases and 251 healthy control persons were genotyped for the G1422A variant (rs1049353) with a TaqMan assay. Anthropometric measures as body weight, BMI, waist and waist-to-hip ratio (WHR) were assessed by classical methods. Fat mass (FM) was measured by bio-impedance. The prevalence of the G1422A variant was not significantly different between cases and controls (OR = 1.056; P = 0.626). In obese women, no meaningful associations between CNR1 genotype and anthropometric parameters were found. In obese men, CNR1 1422 A/A genotype was significantly associated with higher WHR (P = 0.009) and waist circumference (P = 0.008) after adjusting for age and BMI. Fat mass percentage showed an association (P = 0.011) which disappeared after adjusting for age and BMI. A trend for an association was seen for fat mass (unadjusted P = 0.099; adjusted P = 0.033). Our data indicate that the G1422A polymorphism in the CNR1 gene is associated with increased abdominal adiposity in obese men.