Human monocyte factors mediate cartilage matrix degradation by activation of the resident chondrocytes. In the present work, the cartilage matrix-degrading activity of partially purified human monocyte-derived interleukin 1 has been investigated. Human monocyte or blood mononuclear cell culture supernatants were sequentially purified by phenyl-Sepharose and gel filtration chromatography, or by gel filtration chromatography, isoelectric focusing, or chromatofocusing. Column fractions were simultaneously tested by the standard method that defines interleukin 1 activity--costimulation of mouse thymocyte proliferation--and for matrix macromolecule release from living bovine cartilage explants in organ culture. The two activities showed identical profiles in purification steps that would discriminate according to molecular size, hydrophobicity, and net charge. Moreover, the thermal denaturation profiles of the material purified by chromatofocusing could not distinguish between thymocyte proliferating and matrix degrading activities. These results suggest that interleukin 1 which is present in inflammatory synovial fluids may play an important role in the mediation of cartilage damage in chronic inflammatory arthritides.