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To determine the serum levels of matrix metalloproteinase-3 (MMP-3) in patients with systemic sclerosis (SSc) and investigate their clinical significance in this disease, serum samples from 83 patients with SSc and 30 healthy volunteers were examined by a specific enzyme-linked immunosorbent assay (ELISA). There was no significant difference in serum levels of MMP-3 between SSc patients and healthy controls. However, in female patients, there was a significant difference in serum MMP-3 levels between patients subsequently developing accompanying rheumatoid arthritis (RA) and those not developing RA, and patients with increased levels of MMP-3 were more likely to develop RA than those with normal MMP-3 levels. Additionally, arthralgia, elevated CRP, and elevated rheumatoid factor were seen significantly more frequently in patients with increased MMP-3 levels than in those with normal MMP-3 levels. These results suggest that increased serum MMP-3 is a marker for developing RA in SSc patients. SSc patients with increased serum MMP-3 levels need to be followed up carefully because of the risk of developing overlapping RA.