Arterial spin labeling (ASL) is a non-invasive MRI technique that allows the quantitative measurement of perfusion, (regional cerebral blood flow (rCBF)). The ASL techniques use the labeling of the blood, by inverting or saturating the spins of water molecules of the blood supplying the imaged region. When reaching the capillary bed, these will be exchanged with tissue water giving rise to a perfusion-weighted signal. The subtraction of control (without label) from labeled images yields a signal difference that directly reflects the local perfusion. Being a non-invasive method, it can be repeated as many times as needed allowing the brain perfusion variation quantification associated with endogenous and exogenous stimuli. In this study, the authors have evaluated the CBF variation induced by the neural activity during a common motor task. The study was conducted on a Siemens Verio 3T system using a 12-channel head coil and a pulsed ASL Q2TIPS-PICORE sequence with a GE-EPI readout. The sequences were driven in 3D PACE mode for prospective motion correction. Fifteen healthy volunteers were studied using a simple motor task consisting in sequential thumb-digit opposition. Two different functional ASL protocols were used: #1 one perfusion scan was obtained during rest and another one during an equal period of motor task (total scan time ~8 min) (TI1 = 700 ms, TI1s = 1600 ms, TI2 =1800 ms; 91 Interleaved tag and control volumes were acquired; TR/TE = 2500/25 ms and flip angle = 90°; nine contiguous axial slices of 8 mm thickness acquired in-line with the AC-PC axis, positioned from the vertex of the brain to the top of cerebellum; FOV = 256 × 256 mm(2); matrix 64 × 64; gap between the labeling slab and the proximal 18.8 mm) and #2 a block design alternating five 25s periods of motor task with five 25s periods of rest (total scan time ~4 min) (TI1 = 700 ms, TI1s = 1600 ms, TI2 = 1800 ms; 101 interleaved tag and control volumes were acquired; TR/TE = 2500/11 ms and flip angle = 90°; nine contiguous axial slices of 6 mm thickness acquired in-line with the AC-PC axis, positioned from the vertex of the brain to the top of cerebellum; FOV = 256 × 256 mm(2) ; matrix 64 × 64; gap between the labeling slab and the proximal 18.8 mm). The post-processing was performed using FSL (www.fmrib.ox.uk/fsl). The mean CBF values obtained for protocols #1 / #2 were: CBFrest = 61.0 / 69.4 ml/100g/min; CBFactivation = 104.8 / 109.9 ml/100g/min; and CBFvariation = CBFactivation - CBFrest = 43.7 / 40.5 ml/100g/min. The relative perfusion changes during activation [defined as CBFvariation / CBFrest (%)] were 73±6 % and 62±7 % (mean±SE) for protocols #1 and #2, respectively. These results show that both activation vs rest and block design functional protocols were capable to detect consistent variations in perfusion associated with a simple motor task. However, the block design has the advantages of requiring shorter acquisitions, directly comparing rest and activation conditions and allowing the acquisition of simultaneous Blood oxygenation level dependent (BOLD) contrast information, while still providing comparable results with the more conventional activation vs rest protocol. In conclusion, our results indicate that a block design ASL-BOLD protocol may be a preferable approach for the evaluation of perfusion changes to endogenous stimuli.