Cystic Fibrosis is the most common autosomal recessive genetic disease leading to high mortality and morbidity in man. The investigators have conducted research in families whose proband had cystic fibrosis. The following parameters are being investigated: (a) gene frequency estimate; (b) mutation rate; (c) number of loci; (d) penetrance; (e) differential fertility among carriers; (f) linkage analysis; (g) sweat chloride variability in cystic fibrosis families; (h) heterozygote detection (further evaluation of metachromatic granulation; biochemical evaluation of glycoprotein variability and their effect on bioassays involving cilary inactivation). Family records have been carefully evaluated at the grand parent, uncle and aunt, and first cousin level. Data on over 400 families is historically complete and has been rechecked at least once. Sweat chlorides on additional family members as well as extensive genotyping for erythrocyte antigens, enzymes, and genetically determined serum proteins for a total of 14 commonly polymorphic genetic markers are continually collected. Repeated, detailed family information verified within first degree relatives, their spouses and offspring, provide, we believe, the most accurate cystic fibrosis family data available. In addition to the large scale population and linkage studies, several methods for heterozygote detection have been evaluated. Metachromasia in skin biopsies have proven reasonably successful but not cells derived from peripheral blood. Glycoprotein fractions from the serum and saliva are being tested in cilary inactivation tests reported in oyster mollusks and rabbit respiratory epithelium. Related studies of salivary glycoproteins suggest that they may prove useful in heterozygote detection in either biochemical or bioassay studies presently in progress.