Desmosine is a cross-link amino acid unique to elastin. Previous work has shown that during turnover in the body, desmosine is not reused, and that desmosine is not absorbed from the intestine. Instead, all desmosine released in the course of elastin metabolism is excreted in the urine attached to low molecular weight peptides. Therefore, measurement of desmosine in acid-hydrolysates of urine might be used to monitor elastin breakdown in several pathologic states, including pulmonary emphysema. In the present report, we have described a sensitive, highly specific radioimmunoassay capable of detecting as little as 200 pg of desmosine in acid-hydrolysates of urine. The assay was specific for desmosine; cross-reactivity with merodesmosine, isodesmosine, lysine, and mixed amino acids was 0.25%, 0.1%, less than 0.0003%, and 0%, respectively. Twenty-three normal, nonsmoking subjects had a mean 24-hr desmosine excretion of 47 +/- 15 microgram. In a group of smokers with evidence of chronic obstructive disease and/or lung infection, the values for desmosine excretion ranged from 40 to 400 microgram/24 h. Desmosine radioimmunoassay may find application in the study of diseases involving increased destruction of elastin in the body.