A modified radioimmunoassay (RIA) for desmosine in the urine was investigated as a tool for the rapid estimation of lung elastin catabolism. Cystic fibrosis (CF) and oxygen toxicity were chosen as conditions that might show altered elastin destruction. Using an antibody bound to magnetic particles the RIA was adapted to handle large numbers of samples requiring only 50 microliters or urine. The experiments show that it was not necessary to hydrolyze or extract the urine prior to assay and that collecting spot urines and normalizing the data to urine creatinine gives the same interpretation of the data as total desmosine in a 24-hour collection. Urine desmosine levels were elevated in 10 of 16 patients with CF; however, daily fluctuations were considerable in some subjects, varying as much as 5-fold and underlining the importance of assaying several consecutive days of urine in acute disorders for an accurate estimate of desmosine excretion. The RIA for desmosine is a rapid and sensitive assay that requires no sample preparation and could be applied to clinical situations that require large numbers of samples.