Static exercise causes activation of the sympathetic nervous system that results in increased blood pressure (BP) and renal vascular resistance (RVR). The question arises as to whether renal vasoconstriction seen during static exercise is due to sympathetic activation and/or related to a pressure dependant renal autoregulatory mechanism. To address this issue, we monitored renal blood flow responses to two different handgrip (HG) paradigms in 7 kidney transplant recipients (RTX), and in 11 age matched healthy control subjects. Transplanted kidneys are functionally dennervated. Beat-by-beat analyses of changes in renal blood flow velocity (Duplex ultrasound), BP and heart rate were performed during HG in all subjects. An index of RVR was calculated as BP/renal blood flow velocity. In protocol 1, fatiguing HG [40% of maximum voluntary contraction (MVC)] led to significant increases in RVR in both groups. However at end exercise, RVR was more than 4-fold higher in controls as compared with the RTX group (88% vs. 20% increase over baseline; interaction: P < .001). In protocol 2, short bouts of HG (15 s) led to significant increases in RVR at higher workloads (50% and 70% of MVC) in the controls (P < .001). RVR did not rise in the RTX group. In conclusion, we observed grossly attenuated renal vasoconstrictor responses to exercise in RTX in whom transplanted kidneys were considered functionally dennervated. Our results suggest that renal vasoconstrictor responses to exercise in conscious humans are mainly dependent on activation of a neural mechanism.