Cystic fibrosis (CF) is the most common lethal genetic disease affecting the white population in the United States and Europe. The goal of this project is to use recombinant DNA technology to gain the information necessary to design a test for CF gene carriers. In Phase I of the project lymphoblastoid cell lines will be established from members of large CF pedigrees to provide a source of DNA from family members. This DNA will be used in Phase 2 to determine the genotype of each individual using DNA probes that detect restriction fragment length polymorphisms. The chromosomal location of the CF gene will be determined by genetic linkage to such DNA markers. Chromosome specific cloning procedures will then be applied to cloning and characterizing the gene causing CF. This information concerning the CF gene product will be used to design a reliable test for CF gene carriers that could be used to screen all adults in the general population.