Objective: To test for gene-environment interaction with depressive symptoms and family conflict. Specifically, to first examine whether the influence of family conflict in predicting depressive symptoms is increased in individuals at genetic risk of depression. Second, to test whether the genetic component of variance in depressive symptoms increases as levels of family conflict increase. Method: A longitudinal twin design was used. Children ages 5 to 16 were reassessed approximately 3 years later to test whether the influence of family conflict in predicting depressive symptoms varied according to genetic liability. The conflict subscale of the Family Environment Scale was used to assess family conflict and the Mood and Feelings Questionnaire was used to assess depressive symptoms. The response rate to the questionnaire at time 1 was 73% and 65% at time 2. Controlling for initial symptoms levels (i.e., internalizing at time 1), primary analyses were conducted using ordinary least-squares multiple regression. Structural equation models, using raw score maximum likelihood estimation, were also fit to the data for the purpose of model fit comparison. Results: Results suggested significant gene-environment interaction specifically with depressive symptoms and family conflict. Genetic factors were of greater importance in the etiology of depressive symptoms where levels of family conflict were high. The effects of family conflict on depressive symptoms were greater in children and adolescents at genetic risk of depression. Conclusions: The present results suggest that children with a family history of depression may be at an increased risk of developing depressive symptoms in response to family conflict. Intervention programs that incorporate one or more family systems may be of benefit in alleviating the adverse effect of negative family factors on children. (Contains 2 figures and 3 tables.)