Tissue inhibitors of metalloproteinases (TIMP-1 and -2) are common inhibitors of matrix metallo-proteinases (MMPs), thereby blocking degradation of extracellular matrix components. TIMP-1 and -2 have been reported to exhibit inhibitory activities against tumor invasion and metastasis. We measured the serum TIMP-1 levels in 16 healthy volunteers and in 69 patients with bladder cancer using a sandwich enzyme immunoassay, and evaluated the correlation between serum TIMP-1 levels and clinicopathological features. Patients with bladder cancer showed significantly higher serum TIMP-1 levels (251.1 +/- 96.0 ng/ml; p < 0.01) than those of healthy volunteers (168.5 +/- 33.2 ng/ml), and a positive correlation between the TIMP-1 level and invasion and metastasis was observed. This is considered to be the result of the reactive production of TIMP-1 in cancerous tissues. Thus, serum TIMP-1 levels may become a reliable clinical marker of the progression of bladder cancer.