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Many species have distributions that span distinctly different physiographic regions, and effective conservation of such taxa will require a full accounting of all factors that potentially influence populations. Ecologists recognize effects of physiographic differences in topography, geology and climate on local habitat configurations, and thus the relevance of landscape heterogeneity to species distributions and abundances. However, research is lacking that examines how physiography affects the processes underlying metapopulation dynamics. We used data describing occupancy dynamics of stream fishes to evaluate evidence that physiography influences rates at which individual taxa persist in or colonize stream reaches under different flow conditions. Using periodic survey data from a stream fish assemblage in a large river basin that encompasses multiple physiographic regions, we fit multi-species dynamic occupancy models. Our modeling results suggested that stream fish colonization but not persistence was strongly governed by physiography, with estimated colonization rates considerably higher in Coastal Plain streams than in Piedmont and Blue Ridge systems. Like colonization, persistence was positively related to an index of stream flow magnitude, but the relationship between flow and persistence did not depend on physiography. Understanding the relative importance of colonization and persistence, and how one or both processes may change across the landscape, is critical information for the conservation of broadly distributed taxa, and conservation strategies explicitly accounting for spatial variation in these processes are likely to be more successful for such taxa. ; U.S. Geological Survey National Water Census and Ecosystems Mission Area, WaterSMART Program ; We are extremely grateful to the many individuals who helped with field work during this project. At the University of Georgia River Basin Center, Jon Skaggs created Fig. 1 and Doug Leasure provided considerable assistance during model development. Constructive comments from Phillip Bumpers, Duncan Elkins, Greg Jacobs, and two anonymous reviewers substantially improved the manuscript. Use of trade, product, or firm names does not imply endorsement by the U.S. Government. Funding was provided by the U.S. Geological Survey National Water Census and Ecosystems Mission Area, WaterSMART Program. ; Public domain authored by a U.S. government employee