Low perceived social acceptance is a significant risk factor for emotional difficulties in children. No studies, however, have examined genetic factors that may underlie individual differences in perceived social acceptance. In the present study we examined the relation between polymorphisms on the catechol-O-methyltransferase (COMT) Val158Met and serotonin transporter promoter (5-HTTLPR) genes and perceived social acceptance in 103 adolescent girls. Only the COMT polymorphism was related to perceived social acceptance: Val-allele carriers reported greater perceived social acceptance than did homozygous Met-allele carriers. In a subsample of these participants, homozygous Val-allele carriers reported greater maintenance of positive emotions during stress. This, in turn, predicted social acceptance, suggesting that COMT exerts its effects on social functioning through emotion regulation. These data are the first to show an association between COMT and social functioning in children. Future research might profitably examine emotion regulation as a mediator between COMT and social acceptance.