Studies on the relationship between acute-phase protein (APP) production, clinical disease activity and progression of radiological damage in RA have been hampered by three factors: patients are studied at different stages of the disease; APP levels are taken incidentally rather than serially; and inter-individual differences in the relationship between the extent of the acute-phase reaction and the progression of radiological damage are not accounted for. A group of 110 newly diagnosed (complaints < 1 year) patients with RA were analysed for a follow-up period of at least three years. Damage was assessed radiologically according to the modified method of Sharp. As radiological progression is a cumulative event, APP production was also calculated by plotting serial CRP levels over time. Overall, a highly significant correlation was found between CRP production and radiological progression; however, a wide variation was observed due to inter-individual differences. The greatest variation was found in the lower range of CRP values, where inter-individual variation could not be accounted for by HLA-DR4, positive RF, sex or age. In conclusion, the prognostic use of serial measurement of APPs for the assessment of radiological progression is limited due to inter-individual variation. Knowledge of the factors underlying these inter-individual differences will increase the applicability of CRP in the prediction of joint damage for individual patients.