It was reported recently that exposure to an adverse rearing environment lowers central nervous system (CNS) serotonergic activity in a nonhuman primate (rhesus monkeys), but only among animals having the shorter variant of a functional, biallelic repeat polymorphism in the regulatory region of the serotonin transporter (5-HTT) gene. Because repeat variants of the same core sequence affect transcriptional efficiency of the 5-HTT gene in humans, we examined whether biallelic variation in the 5-HTT gene-linked polymorphic region (5-HTTLPR) acts analogously to modulate a previously described association between socio-economic status (SES) and CNS serotonergic function. The 5-HTTLPR was genotyped in 139 adult men and women (n = 75 and 64) who were administered a standard neuroendocrine challenge to assess central serotonergic responsivity (plasma prolactin (PRL) response to the serotonin releasing agent, fenfluramine). Socio-economic status was estimated from reported income and years of education. Hierarchical linear regression showed serotonergic responsivity to be predicted by the interaction of 5-HTTLPR genotype and SES (p = 0.018). Individuals of lower income and less education had lower peak PRL concentrations following administration of fenfluramine than did subjects ranking higher on these dimensions, but only among persons possessing at least one 5-HTTLPR short allele. Within genotype, SES covaried moderately with the PRL response to fenfluramine among subjects who were homozygous for the short allele (r18 = 0.50, p < 0.03). A similar association was present at lesser magnitude in heterozygotes (r70 = 0.24, p < 0.05) and absent among subjects homozygous for the long allele (r45 = -0.04, n.s.). Findings were comparable for men and women and persisted on re-analysis restricted to persons without current Axis I psychopathology. We conclude that allelic variation at 5-HTTLPR moderates the influence of social position on CNS serotonergic responsivity.