BackgroundAmericans of African ancestry are less likely to receive a selective serotonin reuptake inhibitor (SSRI) for treatment of major depressive disorder than Americans of European ancestry. A functional insertion/deletion polymorphism in the promoter of the serotonin transporter (5-HTT) geneSLC6A4has been shown to modulateSLC6A4transcription, affecting response to SSRIs. Several studies in populations of predominantly European ancestry have consistently found that theSLC6A4promoter polymorphism (referred to as the 5-HTT-linked polymorphic region; 5-HTTLPR) long (L) allele is associated with better response to SSRI treatment than the short (S) allele.ObjectiveThe frequency ofSLC6A4(5-HTTLPR) alleles in 865 black Americans and Afro-Caribbeans was examined to assess possible implications for treatment.Study design and methodsSLC6A4(5-HTTLPR) genotypes were determined in individuals with self-identified African ancestry from South Carolina (n = 489), western Pennsylvania (n = 207), and Tobago (n = 169). Frequencies were compared using chi-square analyses.ResultsIt was verified that the L allele is highly prevalent in Americans of African ancestry, ranging from 77% in western Pennsylvania to 87% in South Carolina. The frequency of theSLC6A4-(L) allele is significantly higher in African-Americans than has been reported for European-Americans (typically 56–60%). There are both statistically significant geographic differences and slight deviations from Hardy-Weinberg equilibrium.ConclusionsGiven the potential influence on treatment response, these findings have implications for the use of SSRIs in this population. The results suggest that additional studies to examine the impact of these alleles on treatment response in African-Americans are warranted.