Objective To illustrate the problem of generalizability of epidemiological findings derived from a single population using data from the Rochester Epidemiology Project and from the US Census. Methods We compared the characteristics of the Olmsted County, Minnesota, population with the characteristics of populations residing in the state of Minnesota, the Upper Midwest, and the entire United States. Results Age, sex, and ethnic characteristics of Olmsted County were similar to those of the state of Minnesota and the Upper Midwest from 1970 to 2000. However, Olmsted County was less ethnically diverse than the entire US population (90.3% vs 75.1% white), more highly educated (91.1% vs 80.4% high school graduates), and wealthier ($51,316 vs $41,994 median household income; 2000 US Census data). Age-and sex-specific mortality rates were similar for Olmsted County, the state of Minnesota, and the entire United States. Conclusion We provide an example of analyses and comparisons that may guide the generalization of epidemiological findings from a single population to other populations or to the entire United States.