Background: Empirical studies demonstrate that maternal sensitivity is associated with attachment security in infancy, while maternal frightening/frightened behavior is related to attachment disorganization. However, attachment disorganization is also predicted by individual dispositions in infancy. Indeed, recent studies indicate a link between attachment disorganization and DRD4 gene polymorphisms, thus suggesting a genetic vulnerability for attachment disorganization. The aims of our study were twofold, to test a) a possible direct link between molecular genetic variations and attachment disorganization, and b) a possible gene-environment interaction with a moderating effect of early maternal caregiving. Methods: Attachment security and disorganization, as well as quality of maternal behavior were assessed in the infants of the Regensburg Longitudinal Study IV (N = 106) at the age of 12 months. DNA samples were collected in order to assess the exon III repeat polymorphism in the coding region and the -521 CT single nucleotide polymorphism (SNP) in the regulatory region of the DRD4 gene and a repeat polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene. Results: Significant associations were found between attachment disorganization and the short polymorphism of the serotonin transporter gene. Also, a gene-environment interaction indicated that this genetic association was only valid for infants of mothers exhibiting low responsiveness. No other significant genetic associations with attachment disorganization were apparent. Conclusions: The study suggests a gene-environment interaction whereby biological determinants of attachment disorganization are moderated by social experiences. Different pathways of the development of attachment disorganization are discussed based on a bio-behavioral model of development.