We report three patients with selective topographic disorientation due to small, focal hemorrhages extending from the right retrosplenial region to the medial parietal lobe. All three could discriminate and identify familiar buildings and landscapes, but had great difficulty remembering spatial positional relationships between two distant locations (i.e., the direction from one location to another) in familiar areas. These symptoms were different than the perception and memory deficits for buildings and landscapes caused by the medial temporo-occipital lesion. These findings suggest that the directional orientation between two locations within a familiar area ("sense of direction") is closely associated with the right retrosplenial region and the medial parietal lobe in humans.