A single nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene Val66Met has been associated with depression. However, the relationship between this SNP and depression has been mixed, especially when comparing studies of child and adult depression. We examined whether Val66Met would predict depression differentially in mothers versus their daughters. We also examined whether rumination, the tendency to brood and repetitively think about negative information, might serve as a mediator in the path between genotype and depressive symptoms. Participants included 200 individuals (100 mother-daughter pairs) from a high-risk population. The BDNF Val66Met polymorphism was examined in DNA samples from the mothers and daughters, and measures of depressive symptoms and rumination were also obtained. Among the young adolescent girls (ages 10-14), the Val/Val genotype was associated with more depressive symptoms and higher rumination scores compared to the Val/Met genotype. Furthermore, rumination mediated the relationship between genotype and depressive symptoms. However, in the mothers with adult-onset depression the Val/Met genotype was associated with more depressive symptoms, and rumination again mediated the relationship between genotype and depression. Rumination may be an endophenotype in the pathway from the BDNF Val66Met polymorphism to depression. Future work should further explore this mechanism and pursue explanations for its effects at different times in development.