Data has been presented in support of the prophylactic utilization of a comprehensive therapeutic program for patients with cystic fibrosis. Ninety-eight consecutive patients have been followed for 3 to 7 years (average 4½ years). The course of the disease as shown by the clinical evaluations of General Activity, Physical Examination of the Chest, Nutrition, and Chest X-ray for the 49 of these patients considered to be on prophylactic therapy has been significantly different from the accepted natural course of the disease and from that of the 49 patients who had irreversible pulmonary damage when first seen. Objective data collected on these patients including growth and weight changes, morbidity and mortality experience, and pulmonary function studies showed good correlation with the clinical evaluations. No evidence of significant progression in the pulmonary lesion was observed by any criteria for the prophylactically treated group. Indeed, mean pulmonary function test results for these patients were well within the range of normal values even at the end of the average 4½-year follow-up period at an average age of 7 years. No deaths occurred in this group. The mortality rate of only 2% per year of follow-up, with no deaths under 6 years of age, for the entire group of 98 patients indicates the over-all effectiveness of the therapeutic program. This study supports the need for early diagnosis and the prophylactic approach to treatment.