Macroscale (continental) patterns of vertebrate species richness have been related to a variety of climatic and historical influences. However, within North America and Britain, empirical evidence suggests that climatic energy is most significant. In this analysis, I examine mesoscale patterns of vertebrate species richness within the U.S. State of Wyoming. I test the generality of the species-energy hypothesis in explaining richness at this scale using high-resolution environmental datasets and a geographic information system (GIS). Results provide little evidence to support the hypotheses that mesoscale species richness of vertebrates follows a linear relationship with climatic energy or a hump-shaped relationship with primary productivity. By contrast, vertebrate richness within Wyoming is most strongly associated with variability in vegetation and other aspects of environmental heterogeneity over a range of sampling grains. This result underscores the benefit of protecting a maximum diversity of vegetation and habitat types for biodiversity conservation.