Cystic fibrosis (CF) is the most common lethal genetic disease of Caucasian children. The basic defect is not known nor is there an assay for the CF genotype suitable for genetic counseling. Altered enzyme activities and metabolite levels have been reported in CF patient materials. We have isolated a ciliostatic fraction from CF saliva which inhibits mammalian debranching enzyme. The goal of the proposed research is to determine if the effect of salivary CF factor on enzyme action or secretion is the basis for any of the reported alterations in CF enzyme activities. Fractions corresponding to the factor activity in CF saliva will be isolated form CF homozygote (CF), CF heterozygote (H) and normal (N) saliva samples. The effect of these fractions on erythrocyte membrane ATPase, arginine esterase, glutathaone reductase, diamine oxidase, and other enzymes reported to be altered in CF will be determined. A quantitative assay for the salivary CF factor will be developed based on its effect on enzyme activty. This assay will be used to measure the factor concentration in CF, H, and N saliva. The proposed experiments will define the role of the salivary factor in CF pathogenesi and will determine if salivary factor levels can be used for CF genetic counseling.