1. The purpose of this work was to explore the cortical and subcortical mechanisms underlying the execution of voluntary saccadic eye movements in humans. 2. Normalized regional cerebral blood flow (NrCBF) was measured using positron emission tomography (PET) and H2(15O) bolus intravenous injections in four right-handed healthy volunteers at rest and while performing self-paced voluntary horizontal saccadic eye movements in total darkness. 3. Magnetic resonance imaging of each subject's brain was matched to PET images, allowing the detection of activation in individually defined anatomic regions of interest. Cortical regions were drawn according to gyri limits; subcortical structures were also defined. 4. Self-paced saccadic eye movements elicited bilateral NrCBF increases in the lenticular nuclei, including putamen and globus pallidus, and in the thalamus. At the cortical level, we found bilateral NrCBF increases in the precentral gyrus, the superior part of the median frontal gyrus that corresponds to the supplementary motor area. There was also a significant NrCBF increase in the cerebellar vermis. 5. Right fusiform and lingual gyri, right insula, and left cingulate gyrus were also activated during the execution of saccades. 6. These results indicate that the classical basal ganglia-thalamocortical motor loop previously described for skeletal movements may also be involved in simple saccadic eye movements in humans.