To investigate nutritional growth retardation and the adaptive response to malnutrition in cystic fibrosis (CF), body composition and muscle protein catabolism were studied in nine malnourished CF children and eight healthy controls by anthropometry, measurement of whole body potassium, urinary creatinine excretion, creatinine height index, and urinary 3-methylhistidine excretion, an index of myofibrillar protein catabolism. CF children had a significant deficit of body mass (p less than 0.001), derived from both the body fat and the fat-free compartments, including a deficit in muscle mass (p less than 0.005). A deficit of muscle mass in CF was also reflected by a lower creatinine height index (mean +/- 1 SEM = 0.66 +/- 0.04 in CF, versus 0.85 +/- 0.5 in controls, p less than 0.02). Urinary 3-methylhistidine excretion was elevated in CF children and the mean (+/- 1 SEM) rate of muscle protein catabolism was 0.82 +/- 0.06 versus 0.53 +/- 0.04 kg-1 24 h-1 in CF and controls, respectively (p less than 0.01). 3-Methylhistidine excretion rates did not correlate with severity of disease as assessed by clinical score. We conclude that nutritional growth retardation in CF is characterized by a protein energy deficit resembling that of protein-energy malnutrition, but that in contrast to the normal adaptive response to protein-energy malnutrition, muscle protein catabolism is markedly increased. These data may have important implications regarding the clinical course and prognosis of CF and the design of optimal therapy.