The Interior Lowland of North America, comprising the Central Lowland and the Great Plains, is a region of approximately 3.2 x 106 km2. The nature of the (climatic) climax vegetation in this area has been a matter of controversy. Empirical evidence regarding the vegetation of the region from the Late Tertiary to recent is consistent with the idea that the area can support two types of vegetation, grassland or forest, under broadly the same climatic regime and raises questions regarding vegetation-atmosphere interactions. Positive feedbacks relating to surface hydrology may tend to favor forests; positive feedbacks involving fire regime may tend to favor grasslands. It should be possible to use coupled vegetation-climate models to test the idea that vegetation shifts in this region affect hydrologic processes and climates at scales ranging from local to global. Grassland/forest shifts, and associated differences in fire regimes, may also be useful as representations of the range of natural variability in biogeochemical cycling, particularly during the Holocene.