OBJECTIVE To examine the hypothesis that aggrecan, cartilage oligomeric matrix protein (COMP), and bone sialoprotein (BSP) concentrations in synovial fluid could provide information on variations of progression of joint destruction in rheumatoid arthritis. METHODS Aggrecan, COMP, and BSP were quantified by enzyme linked immunosorbent assays in longitudinally collected knee joint synovial fluid samples of patients rapidly developing destruction in knees or hips, the "'destructive" group, n = 18, and in patients slowly developing destruction, the "non-destructive" group, n = 25. RESULTS The aggrecan concentrations decreased from initially high levels (P < < 0.001), and the BSP concentrations increased (P < < 0.001) over time in the destructive group, whereas levels of both markers were low and did not change in the non-destructive group. The COMP levels did not change in any of the groups. The aggrecan concentrations were initially highest in the group developing destructions (P < < 0.001), whereas no difference between the groups was found regarding levels of COMP or BSP in the first sample. CONCLUSIONS A destructive group was characterised by higher initial aggrecan concentrations and rising BSP concentrations in synovial fluid with time. Quantification of cartilage and bone derived macromolecules contributes to the assessment of extent of tissue destruction and may help in the early identification of patients at risk of rapidly progressing destruction.