Serotonin plays a central role in mood regulation and the development of depressive disorders. The present study investigated whether a functional polymorphism (5HTTLPR) of the serotonin transporter gene interacts with maltreatment in the prediction of depression. A cohort of 17-18 years old students (n = 1,482) anonymously completed the Survey of Adolescent Life and Health in Vestmanland 2006 and gave a saliva sample for DNA extraction. An association between maltreatment and adolescent depression was found independent of sex. When the whole population was analyzed, no main effect of 5HTTLPR in association with depression was found. When separated by sex, a significant main effect and a G x E interaction effect of the SS allele was found among girls. No gene main effect or G x E interaction effect was found among boys. The present study confirms previous findings of sex differences in interaction effects between the 5HTTLPR polymorphism and maltreatment in the prediction of adolescent depression.