The goal of this study is to investigate the relationship between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) and body mass index (BMI) in two sizable and well-characterized populations of British women: the British Women's Heart and Health Study (BWHHS) (age 60-79 years) and the mothers from the Avon Longitudinal Study of Parents and Children (age 16-44 years). We genotyped the Val66Met polymorphism (rs6265) in these two populations, and conducted a linear regression analysis to test for an association between this polymorphism and BMI. Both study populations indicated an association between BMI and the Val66Met polymorphism, with individuals carrying the Met-Met genotype having a lower mean BMI than those with the Val-Met or Val-Val genotypes (in the BWHHS): mean BMI difference=-0.911 kg/m(2), 95% confidence interval (CI): -1.70 to -0.12, P=0.023; in the mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC): mean BMI difference=-0.57 kg/m(2), 95%CI: -1.08 to -0.054, P=0.03). In a pooled analysis of these two studies, together with one further published study that provided data in a suitable format for inclusion in our meta-analysis, we found a pooled difference of -0.76 (95% CI: -1.16, -0.036) for adult women; I(2)-test for heterogeneity=51%, P=0.13. Our study indicated an association between BDNF and BMI in two general population studies of women. The exact role of BDNF in weight regulation merits further investigation.