OBJECTIVES: In this study the serum levels of proMMP-2, active MMP-2, TIMP-2 and MMP-2:TIMP2 complex were evaluated. We also studied the correlation of these parameters with clinicopathological parameters in patients suffering from bladder carcinoma and outcome in this patient group. METHODS: The levels of circulating proMMP-2, active MMP-2, proMMP-9, TIMP-1, TIMP-2 and MMP-2:TIMP-2 complex of 84 patients with bladder cancer were measured by ELISA. The proMMP-2 and TIMP-2 immunoreactive proteins were studied. These results were compared to clinicopathological parameters and patient outcome. RESULTS: Low circulating proMMP-2 levels significantly correlated with poor prognosis. The 5-year disease-specific survival rate was 46% in patients with high levels of proMMP-2 versus 23% in patients with low proMMP-2 levels (p = 0.011). Low TIMP-2 levels could also present as a marker of poor prognosis. In this study, the 5-year disease-specific survival in patients with low circulating TIMP-2 levels was 19% compared to 66% in patients with high TIMP-2 levels (p = 0.004). CONCLUSION: These results indicate that high levels of circulating proMMP-2 and TIMP-2 levels are both associated with a better clinical course; moreover, total proMMP-2 is an independent prognostic marker of bladder cancer progression.