Changes in body composition and muscle protein degradation were studied in seven nutritionally growth-retarded children with cystic fibrosis (CF) before and after nutritional supplementation and in eight healthy children who served as controls. Supplemental feedings consisted of a peptide formula that increased dietary protein and energy intakes approximately 20-40% over a 6-month period, delivered either as oral supplement or overnight intragastric feeding. Body composition was assessed by anthropometric data and measurements of whole body potassium (40K) and creatinine excretion. Muscle protein degradation was measured by urinary 3-methylhistidine excretion, an index of myofibrillar protein catabolism. Compared with controls, CF children had significantly reduced body mass, body fat, and muscle mass, and a significantly increased rate of myofibrillar protein degradation. With nutritional supplementation, significant catch-up weight gain and improved linear growth were observed with evidence of accretion of lean body mass and muscle mass, and in all but one severely malnourished patient with progressive disease, there was normalization of the high rate of muscle protein degradation. Thus, this form of nutritional therapy has significant benefits in terms of body protein accretion and myofibrillar protein degradation.