Previous studies have related aggression and other externalizing problems in children to either dopamine D4 receptor polymorphisms or harsh and insensitive parenting. In this study it was determined whether the combination of the DRD4 7-repeat polymorphism and maternal insensitivity predicted significantly more externalizing behavior in preschoolers. The results pointed to a gene-environment interaction effect: maternal insensitivity was associated with externalizing (oppositional, aggressive) behaviors, but only in the presence of the DRD4 7-repeat polymorphism. The increase in externalizing behaviors in children with the 7-repeat allele exposed to insensitive care compared to children without these combined risks was sixfold. The data indicate that children are differentially susceptible to insensitive parenting dependent on the presence of the 7-repeat DRD4 allele.