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Genes involved in serotonin metabolism are good candidates for the pathogenesis of seasonal affective disorder (SAD). A functional variant in the serotonin transporter promoter, 5-HTTLPR, has recently been shown to be associated with SAD and seasonality. The purpose of this study was to determine whether− 1438G/A, a polymorphism in the 5-HT 2A promoter, is associated with SAD and seasonality, and whether it has additive effects with 5-HTTLPR on seasonality. Sixty-seven individuals with SAD and 69 normal volunteers, all screened with the SCID and diagnosed according to DSM-III-R criteria, were genotyped for the− 1438G/A 5-HT 2A promoter polymorphism. All had been previously genotyped for 5-HTTLPR and had been assessed for seasonality by the Global Seasonality Scale. There was a significant increase in the frequency of the− 1438A variant allele of the 5-HT 2A promoter polymorphism in SAD …