A magnetization transfer (MT)-prepared echo-planar imaging (EPI) pulse sequence was developed to study motor cortex activation, using a finger tapping paradigm. MT weighting resulted in a reduction of both the activated area and, in the majority of activated pixels, the functional MRI signal, regardless of the correlation coefficient threshold used in generating the activation map. The magnetization transfer ratio (MTR) was higher during task activation than during rest. Because the MT effect is strongly tissue-dependent, these results support the hypothesis that incorporation of MT into functional MRI will help to understand the origin of the functional MRI signal.