Objective. To evaluate the significance of serum matrix metalloproteinase-3 (MMP-3) levels in relation to the development of radiological damage (X-ray damage) in early rheumatoid arthritis (RA). Methods. Serum MMP-3 levels were measured in 46 healthy controls (CTRL), 19 osteoarthritis (OA) and 78 RA patients with joint symptoms for <1 yr at presentation (TO): 48 patients without and 30 with X-ray damage at TO. Serum MMP-3, measured by ELISA, and X-ray damage, scored according to Sharp's method, were assessed at 0, 6, 12 and 24 months. Results. MMP-3 levels in CTRL and OA were low or undetectable with no differences between the groups (P = 0.19). Levels in RA were higher than in CTRL (P < 0.01). Initial MMP-3 levels in patients with X-ray damage at T0 (n = 30) were higher than the levels in patients without any X-ray damage during follow-up (n = 19) (P < 0.01), but were not different from those in patients who developed X-ray damage during the study (n = 29) (P = 0.11). In the patients without X-ray damage at T0, there was a significant correlation between MMP-3 at TO and the total X-ray damage after 6 months (r = 0.34, P = 0.02) and 12 months (r = 0.32, P = 0.03). This correlation was almost exclusively determined by joint space narrowing in the Sharp score. Conclusion. The serum MMP-3 level seems to be an indicator for the development of radiological damage in patients with early RA and appears to be particularly indicative of cartilage degradation.