We investigated the relationship of the gene for the X-linked orphan G protein-coupled receptor (GPR50) to childhood-onset mood disorders in a sample of 384 families with 468 affected children and adolescents collected in Hungary. Our choice of this gene for study was based on a previous report of an association of GPR50 with bipolar disorder and major depressive disorder. A significant association with the deletion allele of an insertion/deletion polymorphism (Delta502-505) located in exon 2 had been reported in a sample of 226 patients with major depressive disorder and 264 patients with bipolar disorder. The association was more significant in females compared with males in those samples. We used for this study a polymorphism in complete linkage disequilibrium with the Delta502-505 polymorphism, Thr532Ala (rs561077), and two additional polymorphisms, Val606Ile (rs13440581) and an intronic polymorphism (rs2072621). We found no evidence for an association for the markers analyzed individually, nor for haplotypes of these markers. Further, we found no evidence of association when the results were analyzed in girls only (n=215). We, therefore, failed to replicate the previous association of this gene with mood disorders.