Purpose: There is some speculation about geographic differences in physical activity (PA) levels. We examined the prevalence of physical inactivity (PIA) and whether US citizens met the recommended levels of PA across the United States. In addition, the association between PIA/PA and degree of urbanization in the 4 main US regions (Northeast, Midwest, South, and West) was determined. Methods: Participants were 178,161 respondents to the 2000 Behavioral Risk Factor Surveillance System (BRFSS). Data from 49 states and the District of Columbia were included (excluding Alaska). States were categorized by urban status according to the US Department of Agriculture. Physical activity variables were those commonly used in national surveillance systems (PIA = no leisure-time PA; and PA = meeting a PA recommendation). Results: Nationally, PA levels were higher in urban areas than in rural areas; correspondingly, PIA levels were higher in rural areas than in urban areas. Regionally, the urban-rural differences were most striking in the South and were, in fact, often absent in other regions. Demographic factors appeared to modify the association. Conclusion: The association between PA and degree of urbanization is evident and robust in the South but cannot be generalized to all regions of the United States. For the most part, the Midwest and the Northeast do not experience any relationship between PA and urbanization, whereas, in the West, the trend appears to be opposite of that observed in the South.