Objective: Renal sympathetic innervation is important in the control of renal and systemic hemodynamics and a target for pharmacological and catheter-based therapies. The effect of a physiological sympathetic stimulus using static handgrip exercise on renal hemodynamics and intraglomerular pressure in humans is unknown. Design and method: We recorded renal arterial pressure and flow velocity in patients with a clinical indication for coronary or peripheral angiography using a sensor-equipped guidewire during baseline, handgrip, resting, and hyperemia following intrarenal dopamine (30 ug/kg). Changes in perfusion pressure were expressed as delta mean arterial pressure, changes in flow velocity as percentage with respect to baseline. Intraglomerular pressure was estimated using a Windkessel model. Results: We included 18 patients with median age 57 years (range 27–85), 61% male in the final analysis. An overview of the hemodynamic responses is given in Figure 1. During static handgrip mean renal arterial pressure increased by 15.2 mmHg (range 4.2–53.0), while flow decreased by 11.2%, but with large variation between individuals (range -13.4–49.8%). Intraglomerular pressure increased with 4.2 mmHg (range -3.9–22.1). Flow velocity under resting conditions remained stable with median 100.6% (range 82.3–114.6) compared to baseline. During hyperemia, maximal flow was 180% (range 111–281), while intraglomerular pressure decreased to 33.0 mmHg [IQR 26.7–39.8]. Changes in renal pressure and flow during handgrip exercise were correlated (rho = -0.68; p = 0.002). Conclusions: We show that there are significant variations in the response to sympathetic stimulation following static handgrip exercise using invasive renal arterial measurements. These results demonstrate that intra-arterial renal hemodynamic measurements can be used to determine the renal effect of systemic sympathetic stimulus and allows identification of patients with higher and lower sympathetic control of renal perfusion. This may be useful in determining the response to therapeutic interventions aimed at altering renal sympathetic control.