The serum anticollagen antibodies to collagen types II, IX, and XI, as well as the antibody level to chondrocyte membrane extract were investigated in patients suffering from severe osteoarthritis (n = 86) in comparison with patients free of primary arthritis (n = 33) and with control healthy patients (n = 44), respectively. Isolation and purification of cartilage antigens and their relevance to ELISA reaction have been outlined. Although the method for anticollagen antibodies to types IX and XI was more sensitive than that of type II, its sensitivity was very low (52%). The determination of the specific IgG fraction by affinity chromatography seemed to be more sensitive: in osteoarthritic patients the percentage of the "arthritogen" IgG rose to 10% of the total IgG. The determination of antibody level against chondrocyte membrane extract was adapted to human diagnostic purposes. In osteoarthritic patients the serum antibody level was significantly higher than in healthy controls. The specificity of this new test was proved by the facts that: (a) only the collagen-binding fraction of the membrane extract reacts with the patient's sera; (b) the ELISA reaction could be totally inhibited by the antigen; (c) patients suffering from noninflammatory joint diseases were characterized by low antibody levels.