A B S T R A C T Urinary excretion of hydroxyproline (Hyp) is one index of total collagen degradation, from all sources. Since some of the Hyp released from collagen may be further metabolized before it is excreted, other markers are necessary to measure collagen breakdown. Excretion of the glycosides of hydroxylysine (Hyl), glucosyl galactosyl hydroxylysine (Hyl[GlcGal ]), and galactosyl hydroxylysine (Hyl-[Gal]), more accurately reflects collagen metabolism since these products occur in specific ratios in different tissue collagens and are themselves metabolized only to a minor degree.The ratios of total Hyl/Hyp and Hyl(GlcGal)/Hyl-(Gal) were measured in the urine of normal subjects and of patients with Paget's disease of bone, hyperphosphatasia, and extensive thermal burns. In patients with extensive thermal bums the pattern of urinary Hyl and its glycosides was consistent with degradation of collagen in dermis and fascia. When sorption was decreased stufficiently with calcitonin or disodiuim etidronate in these patients, both the urinary ratios of Hyl/Hyp and Hyl(GlcGal)/Hyl(Gal) rose. In normal subjects treated with calcitonin and excreting relatively little Hyp, the ratio of Hyl/Hyp approached 0.7 and Hyl(GlycGal)/Hyl(Gal) approached 3.5. These increased ratios reveal the existence of a source of collagen breakdown other than skin or bone. The first subcomponent of complement, Cl(q, which has collagen-like sequences, relatively high amounts of Hyl, and most of the glycosylated Hyl as Hyl(GlcGal), could be the source of these metabolites.