We report a 55-year-old right-handed man who presented with topographical disorientation following left retrosplenial hemorrhage. His directional information about familiar places, encoded by previous navigation, was severely impaired, and he could not learn the direction to new places in large-scale spaces beyond the range of visual surveillance. By contrast, he had no difficulties with directional information encoded in a tabletop manner: he could locate major cities or countries on a map, and he also could memorize the spatial relationship of objects in a room. Six months after the ictus, when he had recovered from his directional disorientation, a functional magnetic resonance imaging (fMRI) study of mental navigation demonstrated prominent activation in the retrosplenial area along the right parieto-occipital sulcus and the circumference of the injured area on the left side. The present study, together with previous investigations including clinical case reports, functional neuroimaging, and anatomical and physiological studies on monkeys, suggests that the 'sense of direction' in a large-scale locomotor environment is subserved by the visual area along the parieto-occipital sulcus, and that bilateral deterioration of this function causes directional disorientation.