We have earlier reported that season of birth interacts with the hypofunctional 7-repeat (7R) allele of the dopamine-4 receptor gene (DRD4) to promote weight gain and obesity in women with seasonal affective disorder (SAD). This study examined whether this gene-environment interaction influences body weight regulation in women with bulimia nervosa (BN). In 188 female probands with BN, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) using season-of-birth, DRD4 genotype (7R present/absent), and past history of anorexia nervosa (yes/no) as independent variables, and age at maximum weight as the co-variate. Consistent with our SAD study, the birth-season x DRD4 interaction was a significant predictor of maximal BMI. Although in SAD, the spring-birth/7R+ group had markedly elevated maximal BMIs and high rates of obesity, in this BN sample, the fall-birth/7R+ group exhibited the highest BMI values (N=17: mean maximal BMI=28.2 kg/m(2) (SE 0.9) vs 25.2 kg/ m(2) (SE 0.3) for all other probands combined (N=171); p=0.002). The lifetime rate of obesity (BMI>30) was also higher in the fall-birth/7R+ vs 'other' group (29.9 vs 8.8%, respectively, p=0.008). These data offer further evidence that season of birth interacts with the 7R allele of DRD4 to influence body weight regulation in female overeating populations.