Description: Background:  Peripheral immunoregulation depends on T regulatory cell trafficking into the allograft in order to modulate the local alloresponse. Little is known about the relevance of trafficking receptors for Tregs after solid organ transplantation in humans. In this study expression of the peripheral chemokine receptors CXCR3 and CCR5 on CD4 + FOXP3 + Treg cells subsets was analyzed and correlated with allograft function in renal transplant recipients. Methods:  Flow cytometry analysis of peripheral blood mononuclear cells of 54 renal transplant recipients receiving a calcineurininhibitorbased immunosuppression was performed for CD4, CD25, FOXP3, and CXCR3 and CCR5 within the first 18 months posttransplantation. Correlation analysis of chemokine receptor expression and glomerular filtration rate as calculated by MDRD (eGFR) was performed. Results:  Expression of the peripheral homing receptors CXCR3 (r=0.44, p〈0.05) and CCR5 (r=0.45, p〈0.05) on FOXP3 + Tregs correlated with renal allograft function (eGFR) in patients receiving tacrolimus (n=28), but not CsA (n=26). CsA but not tracrolimus reduced surface expression of CXCR3 on FOXP3 + Tregs in renal transplant recipients as correlated to trough levels (r-0.42, p〈0.05). In contrast to CD4 + CXCR3 + CD25 lo T cells, flow sorted CD4 + CXCR3 + CD25 hi Tregs isolated from healthy individuals did not produce IFNγ or IL-17 ex vivo and expressed high levels of GARP mRNA both at baseline as well as after TCR activation indicating functional regulatory activity. Conclusion:  Expression of the peripheral trafficking receptors CXCR3 and CCR5 on FOXP3 + Tregs is associated with renal allograft function. These results suggest that Treg trafficking may also depend on the interaction of CXCR3 or CCR5 and their respective ligands.