Research consistently chronicles a variety of mental health difficulties that plague institutionally reared children, including attention-deficit/hyperactivity disorder (ADHD), even if not all institutionalized children evince such problems. In seeking to extend work in this area, this research on gene × environment (GXE) interplay investigated whether the effect of the quality of institutional care-most notably, caregiver intrusiveness-on ADHD symptoms is moderated by the serotonin transporter (5-HTTLPR) polymorphism. One hundred and twenty-seven institutionalized preschoolers were evaluated using the Child Behavior Checklist. Caregiver-rated attention problems and hyperactivity were unrelated to both 5-HTTLPR polymorphism and caregiver intrusiveness. A significant GXE effect, independent of age at placement or duration of institutionalization, emerged, however, consistent with the differential-susceptibility hypothesis: s/s homozygotes manifest the most and least ADHD symptoms when they experienced, respectively, more and less intrusive caregiving. These results provide new insight into the reasons why some institutionalized children, but not others, exhibit ADHD symptoms.