Femoral and tibial cartilage specimens from nonoperated, sham operated, and partially meniscectomized knees of New Zealand white rabbits were studied, using fluorescein-conjugated mouse IgG or 3 monoclonal antibodies (2G2, 2E9, and 6C9) that portrayed differing fine antigenic specificity for rabbit cartilage proteoglycan monomer. In nonoperated and sham operated animals, monoclonal antibodies 2G2 and 2E9 stained cellular/pericellular (C/PC) and matrix areas; antibody 6C9 stained only C/PC areas. Augmented C/PC and matrix staining of osteoarthritic femoral cartilage occurred with 2G2 and 6C9; tibial cartilage staining was reduced. Increased 2E9 staining of C/PC regions was seen in tibial cartilage. The differential staining patterns indicate that proteoglycan macromolecular changes occur in experimental osteoarthritis and that these monoclonal antibodies can be utilized as probes for the connective tissue changes observed.