The renal inflammatory response is regulated by the dopamine receptor D2 (D2R) and its function is impaired in the presence of DRD2 gene variants rs6276/rs6277 (SNPs). Recent reports suggest that sex plays a role in the inflammatory response. We hypothesized that sex and sex hormones affect the D2R-mediated renal inflammatory response. We studied human renal proximal tubule cells (hRPTCs) genotyped for the presence or absence of SNPs. Four cell lines were studied: 2 from female (F) or male (M) subjects not bearing SNPs (wild type [WT]) and 2 from female or male subjects bearing SNPs. We measured mRNA and protein expression of D2R, markers of inflammation (TNF-α, TGF- β1), markers of fibrosis (FN1), injury (Kim-1), and cell proliferation (Ki-67). D2R expression was highest in FWT than in FSNPs, MWT or MSNPs (P<0.02; n=3/group). By contrast TNF-α, TGF- β1, FN1, Kim-1, and Ki-67 expressions were highest in MSNPs than in any of the other group (P<0.05). To assess the effect of the presence of hormones in fetal bovine serum (FBS), we cultured the cell lines in media containing charcoal stripped FBS for 24 h. In the absence of hormones, D2R expression was even higher in FWT (P<0.05), indicating that hormones inhibit the expression of the receptor; there were no significant differences in the other groups, suggesting that the decreased D2R expression due to the presence of SNPs is not hormone-related. The expressions of TNF-α, TGF- β1, and Kim-1 were higher (P<0.05) in MSNPS than in the other groups indicating that either the decreased D2R expression or the presence of hormones per se inhibits the expression of these factors. The expression of Ki-67, however, was decreased in all groups in the absence of hormones (P<0.05), indicating that hormones are necessary for cell proliferation. These results show not only that even in in vitro experiments cells derived from males have a greater response of proinflammatory factors than cells derived from females but also that in hRPTCs the presence of the D2R SNPs imparts an inflammatory phenotype, and that this impairment is dependent on sex and presence of hormones.