Despite the fact that cystic fibrosis (CF) is the most common lethal hereditary disorder of caucasians, there are often delays in diagnosis and referral to centers providing comprehensive care. Thus, there has been a great deal of interest in establishing a reliable method for early detection. A recent advance that appears promising involves measurement of immunoreactive trypsinogen (IRT) on surplus neonatal blood collected for genetic screening. Although generally considered beneficial, newborn screening programs have also caused errors, miscommunication/misunderstanding and stigmatization. Furthermore, it has not been established in a controlled study that early treatment achieved by neonatal diagnosis will be generally cost-effective and medically beneficial for CF patients, (particularly in regard to the chronic lung disease which generally determines a patient's prognosis). Because the efficacy of early treatment of CF patients is controversial, it is important to perform a controlled study of both benefits and risks before mass screening is instituted in the USA for this disease. We propose to randomly screen half the newborn population of Wisconsisn for three years using the IRT test on dried neonatal blood spots and therefore generate an early diagnosis/treatment group. The other half of the population (control group) will have a "blind" IRT assay performed during the neonatal period, but the results will not be computed until the child is 42 months old; prior to that time, CF will be diagnosed based on symptoms or a positive family history. This will allow complete evaluation of the two populations beginning with 4 year old children (the current average age of diagnosis in Wisconsin). Special attention will be given to objective evaluation of pulmonary disease in the two groups and to assessment of potential psychosocial problems in the screened population. Hypotheses to be tested include the following: 1) the majority of CF patients can be diagnosed as neonates by the IRT test; 2) the process of early diagnosis (screening and sweat testing) will not have harmful psychosocial impact; 3) diagnosis in early infancy will prevent malnutrition and growth retardation; and 4) those diagnosed with CF as neonates will have less pulmonary disease than age-matched patients in the control population.