The neural mechanisms underlying ground-level spatial navigation have been investigated, but little is known about other kinds of spatial navigation. Functional magnetic resonance imaging was used to identify differences in brain activation for two types of spatial information, information from the ground-level perspective (route) and information from a global perspective (survey). Participants were scanned during the encoding of two different virtual reality environments, one from each perspective. Comparisons of brain activation during route and survey encoding suggested that both types of information recruited a common network of brain areas, but with important differences. Survey encoding recruited a subset of areas recruited by route encoding, but with greater activation in some areas, including inferior temporal cortex and posterior superior parietal cortex. Route encoding, in contrast, recruited regions that were not activated by survey encoding, including medial temporal lobe structures, anterior superior parietal cortex, and postcentral gyrus. These differences in brain activation are associated with differences in memory performance for the two types of spatial information and contribute to specification of brain components of spatial knowledge.