The sympathetic neural regulation of the cerebral circulation remains controversial. The purpose of the present study was to determine how exercise modulates the simultaneous responsiveness of the cerebral and brachial circulations to 'endogenous' sympathetic activation (cold pressor test). In nine healthy subjects, heart rate (HR) and mean arterial blood pressure (MAP) were continuously measured during cold pressor tests (4°C water) conducted at rest and during randomized bouts of rhythmic handgrip of 10, 25 and 40% of maximal voluntary contraction. Doppler ultrasound was used to examine brachial artery blood flow (FBF) and middle cerebral artery (MCA) mean blood velocity (V mean), and indices of vascular conductance were calculated for the brachial artery (forearm vascular conductance, FVC) and MCA (cerebral vascular conductance index, CVCi). End-tidal PCO2 (P ET.CO2) was evaluated on a breath-by-breath basis. Handgrip evoked increases in HR, FBF, FVC and MCA V mean (P < 0.05 versus rest), while MAP and CVCi were unchanged and P ET.CO2 fell slightly (P < 0.05 versus rest). Increases in MAP and HR during the cold pressor test were similar at rest and during all handgrip trials. Forearm vascular conductance was markedly reduced with the cold pressor test at rest (-45 ± 8%), but this vasoconstrictor effect was progressively attenuated with increasing exercise intensity (FVC -17 ± 3% during exercise at 40% of maximal voluntary contraction; P < 0.05). In contrast, the small reduction in CVCi with cold pressor test was similar at rest and during handgrip (approximately -5%). Our data indicate that while the marked vasoconstrictor responses to sympathetic activation in the skeletal muscle vasculature are blunted by handgrip exercise, the modest cerebrovascular responses to a cold pressor test remain unchanged.