1. Extraretinal modulation of neuronal activity in the human brain was assessed indirectly by measuring changes in regional cerebral blood flow (rCBF) during the execution of large horizontal saccades in complete darkness. With the use of positron emission tomography, rCBF was measured in 9 volunteers as they made 40, 60, 80, 100, 110, 120, or 140 saccades during 60-s scans. 2. With increasing numbers of saccades, rCBF increased in the following oculomotor structures: the frontal eye field, the superior colliculus, and the cerebellar vermis. In parallel to these rCBF increases, rCBF decreased in the striate cortex, adjacent extrastriate cortex, and the parietal cortex. 3. The observed rCBF decreases most likely indicate a decline in the net amount of excitatory neurotransmission in the visual cortex and, as such, may represent a neural substrate of saccadic suppression.