Introduction It remains unlcear whether the main source for vascular resistance in the brain is located in the major cerebral arteries or the smaller arterioles1. Here we use our recently introduced non-invasive measurement of cerebral arterial compliance (AC) to measure the cerebrovascular response to post exercise ischemia (PEI) over the cerebrovascular tree2. AC is inversely related to cerebrovascular resistance; if AC decreases vascular resistance increases. The aim of this study is to investigate where in the cerebral arterial tree AC decreases during PEI, when blood pressure and sympathetic nerve activity are elevated. Data acquisition 8 healthy young men underwent an MRI scan session in which two AC measurements (one rest, one PEI) were done. PEI was induced following isometric forearm contraction (IFC) at 40% of each participant’s maximum grip (3 mins). After 2 mins of IFC, a blood pressure cuff was inflated to 100 mmHg above systolic BP, on the gripping arm, to induce PEI. During PEI (10 mins), pulsed arterial spin labelling (ASL)3 with 32 tag-control pairs for each of seven inversion times (250-850 ms, 100 ms spacing) was performed. Cardiac traces were monitored with a probe at the left index finger. Muscle sympathetic nervous activity (MSNA) in rest and during IFC was measured in a separate session with microneurography of the peroneal nerve in the lower leg. In both sessions (MRI and microneurography) blood pressure was monitored at the left thumb. Data analysis ASL tag and control images were retrospectively grouped according to their acquisition time relative to the cardiac cylce. Maps of diastolic and systolic arterial blood volume (aBVDia and aBV­Sys) were calculated by voxelwise fitting of an arterial input function4 to the average difference signal over time. Average pulse pressure was used to obtain maps of AC (%/mmHg) according to: AC = 100 * (aBVSystole – aBVDiastole) / (aBVDiastole * PP). Regional median AC values were drawn for the flow territories encompassing the major brain feeding arteries, which are the internal carotid and basilar arteries (ICA, BA), and the bilateral middle cerebral arteries (MCA). Results Mean arterial blood pressure and MSNA were significantly increased (paired t-test, p < 0.05) during PEI compared to rest (+9.2 ± 10.6 mmHg and +10.5 ± 7.8 burst/100 heartbeats, respectively). Figure 1 illustrates that during PEI the arteries inferior to and at the level of the Circle of Willis show a decrease in AC, while the MCA flow territories distal from the Circle of Willis show no change in AC. Implications The increase in cerebrovascular resistance (decrease in AC) in the ICA and BA is caused by an increase in vascular smooth muscle cell tone in the arterial walls. This result suggests that the major cerebral arteries proximal to the circle of Willis play an important role in determining cerebral vascular resistance in humans.