The neural basis of navigation by humans was investigated with functional neuroimaging of brain activity during navigation in a familiar, yet complex virtual reality town. Activation of the right hippocampus was strongly associated with knowing accurately where places were located and navigating accurately between them. Getting to those places quickly was strongly associated with activation of the right caudate nucleus. These two right-side brain structures function in the context of associated activity in right inferior parietal and bilateral medial parietal regions that support egocentric movement through the virtual town, and activity in other left-side regions (hippocampus, frontal cortex) probably involved in nonspatial aspects of navigation. These findings outline a network of brain areas that support navigation in humans and link the functions of these regions to physiological observations in other mammals.