Previous studies have related attachment disorganization in children to either dopamine D4 receptor polymorphisms or maternal unresolved loss or trauma and frightening or anomalous parenting. In this study it was examined whether the interaction between genetic (DRD4 7-repeat and -521 C/T) and environmental risk factors (maternal unresolved loss/trauma and maternal frightening behavior) was associated with infant disorganization. A moderating role of the DRD4 gene was found. Maternal unresolved loss or trauma was associated with infant disorganization, but only in the presence of the DRD4 7-repeat polymorphism. The increase in risk for disorganization in children with the 7-repeat allele exposed to maternal unresolved loss/trauma compared to children without these combined risks was 18.8 fold. Similar moderating effects were not found for maternal frightening behavior. Our findings indicate that children are differentially susceptible to unresolved loss or trauma dependent on the presence of the 7-repeat DRD4 allele.