The identification of different mutations that cause cystic fibrosis in the people of Kansas and Oklahoma has been performed by examining 124 independent cystic fibrosis genes for the 14 most commonly mutated loci. The ΔF508 3bp deletion represented 79% of the alleles, and 7% of the remaining alleles were found to harbor the mutations of R553X, G542X, or G551D. None of the remaining 10 common mutations were identified. This pattern of results contrasts with the patterns found in major cities of the United States. The ethnic diversity in these cities is much greater than in the southern Midwest region, and the remaining mutations, therefore, may represent specific ethnic contributions absent in the Midwest population studied. These results directly affect the counseling given to the Midwest patient and impact on any strategies for screening.