T-cells have been implicated in the pathogenesis of renal ischemia reperfusion injury (IRI). To date existing data about the role of the T-cell receptor (Tcr) are contradictory. We hypothesize that the Tcr plays a prominent role in the late phase of renal IRI. Therefore, renal IRI was induced in /, Y/ T-cell-deficient and wild-type mice by clamping renal pedicles for 30 min and reperfusing for 24, 48, 72 and 120 hours. Serum-creatinine increased equally in all three groups 24 hours after ischemia, but significantly improved in Tcr-deficient animals compared to wild-type controls after 72 hours. A significant reduction in renal tubular injury and infiltration of CD4⁺ T-cells in both Tcr-deficient mice compared to wild-type controls was detected. Infiltration of / T-cells into the kidney was reduced in Y/ T-cell-deficient mice until 72 hours after ischemia. In contrast, Y/ T-cell infiltration was equal in wild-type and / T-cell-deficient mice, suggesting an interaction between / and Y/ T-cells. Data of Y/ T-cell deficient mice were confirmed by in vivo depletion of Y/ T-cells in C57BL/6 mice. Whereas / T-cell-deficient mice were still protected after 120 hours, Y/ T-cell deficient mice showed a "delayed wild-type phenotype" with a dramatic increase in kidney infiltrating / Tcr-expressing, CD4+ T-cells. This report provides further evidence that / T-cells are major effector cells in renal IRI, whereas Y/ T-cells play a role as mediator cells in the first 72 hours of renal IRI.