Newly synthesized and endogenous proteoglycan was isolated from human femoral head osteochondrophytic spurs. 35SO4-containing keratan sulphate was measured by its susceptibility to endo-beta-D-galactosidase (keratanase) and comprised 15-17% of the two subpopulations of a proteoglycan monomer fraction (D1) resolved by Sepharose CL-2B chromatography (Kav (I), 0.22; (II), 0.78). The size of the newly synthesized keratan sulphate in these fractions was large (Mr greater than 7,000). The hydroxylamine cleavage product of a proteoglycan aggregate fraction (A1) which eluted in the void volume of a Sepharose CL-2B column was immunoreactive with an anti-keratan sulphate monoclonal antibody, 5-D-4. Unlike the proteoglycan aggregate A1 fraction from bovine nasal cartilage, immunoreactivity against 5-D-4 was also found in chromatographic fractions retarded by Sepharose CL-2B. These results lend additional support to our assertion that the osteophyte extracellular matrix consists of hyaline cartilage-type proteoglycan. Stimulation of osteophyte proliferation may be useful as a repair mechanism for resurfacing denuded areas of osteoarthritic femoral heads.