Single-photon emission computed tomography (SPECT) was used to investigate the feasibility of the technetium 99m-hexamethylpropyleneamineoxime ( 99mTc HM-PAO) split-dose method to evidence changes in regional cerebral blood flow during a motor activation task, in comparison with a quantitative method using the inhalatory xenon-133. Four subjects were studied twice with both methods, at rest and during finger opposition movements. On the activated cerebral hemisphere, a significant increase in regional cerebral blood flow was observed over the motor cortical areas. The average increases were +28.1 +/- 5.6% for the xenon-133 method and +12.3 +/- 5.2% for the 99mTc HM-PAO method. By using the linearization algorithm for the 99mTc HM-PAO method, a mean increase of +22.5 +/- 8.9% was calculated. This study demonstrated that the split-dose method allows the motor activation SPECT studies with 99mTc HM-PAO to be done in a single session.