The regulation of cerebral perfusion during exercise involves metabolic, hemodynamic, neurohumoral and neurogenic factors (Secher et al. 2008). While a sympathetic innervation of the cerebral vasculature has been identified (Duckles, 1983), the influence of sympathetic stimulation on the cerebral circulation is controversial (Secher et al. 2008). The aim of the present study was to simultaneously evaluate the effects of sympathetic stimulation, produced by a cold pressor test (CPT), on the cerebral and brachial circulations both at rest and during handgrip exercise in humans. In 6 healthy subjects (5 men; 20±3 years, mean±SE) the cardiovascular and cerebrovascular responses to CPT (4°C) were examined at rest and during rhythmic handgrip exercise performed at 10, 25 and 40% of maximum voluntary contraction (MVC). Heart rate (HR; ECG) and mean arterial blood pressure (MAP; Portapres) were continuously measured. Stroke volume (SV) was determined off-line (Modelflow) and cardiac output (CO) calculated (CO=HR×SV). Brachial artery blood flow to the exercising forearm (FBF; Doppler ultrasound) and contralateral middle cerebral artery (MCA) mean blood velocity (Vmean; transcranial Doppler ultrasound) were monitored throughout. Forearm vascular conductance (FVC=FBF/MAP) and cerebral vascular conductance index (CVCi=MCA Vmean/MAP) were calculated. End-tidal PCO2 (PETCO2) was evaluated on a breath-by-breath basis. Statistical analyses were performed using repeated measures analysis of variance. Rhythmic handgrip exercise evoked increases in HR, FBF, FVC and MCA Vmean (P<0.05), while MAP and CVCi were unchanged (P>0.05). CPT evoked similar increases in MAP at rest and during all handgrip trials (~8 mmHg), while FBF was reduced. CPT elicited a -55±11% change in FVC (i.e. vasoconstriction) at rest, however the magnitude of this reduction in FVC was progressively attenuated with increasing exercise intensity (-42±11, -30±8 and -18±4%, during handgrip at 10, 25 and 40% MVC, respectively; P<0.05). In contrast, MCA Vmean was unchanged during CPT, and the small reduction in CVCi with CPT was similar at rest and during handgrip (-7±3, -5±3, -7±2 and -8±2%, during rest and handgrip at 10, 25 and 40% MVC, respectively). Small, but significant reductions in PETCO2 (~1 mmHg) were noted from rest to exercise, and with CPT (P<0.05). CO tended to increase with handgrip (P=0.09), but was unchanged with CPT. These preliminary data indicate that the vasoconstrictor responses to sympathetic stimulation with CPT are blunted in the vasculature of the exercising skeletal muscle (functional sympatholysis), while in contrast, CPT appears to evoke only minimal cerebrovascular responses both at rest and during rhythmic handgrip exercise.