The location of the human cortical substrate underlying simple horizontal saccadic eye movements was investigated using echoplanar functional magnetic resonance imaging (fMRI) in young healthy volunteers. Echoplanar imaging with signal targeting and alternating radiofrequency (EPISTAR), a novel perfusion technique, measured signal intensity changes in one to four contiguous 10-mm slices centered to include both striate cortex and putative frontal eye fields during horizontal saccade and fixation conditions. Subtraction images of self-paced visually guided saccadic versus fixation conditions showed bilateral marked and statistically significant localized signal increases in the precentral region (Brodmann areas 4, 6) and peristriate cortex (areas 17, 18, 19) and qualitative increases in the superior medial frontal region, as identified by a Talairach-Tournoux generalized template in the brain slices that were scanned. Additional parietal activation occurred during a target-guided saccade task. Our data (i) support the localization of the human FEF, as identified by simple, nonexploratory saccadic eye movements, in the precentral motor strip and premotor cortex, (ii) show individual variability in the exact anatomical location of saccade-related activations, and (iii) confirm that the EPISTAR technique can demonstrate localized signal increases during a behavioral task.