Mortality in gastric cancer is related to invasion and metastasis. Evidence has accumulated that invasion and rnetastasis in solid tumors require the action of tumor associated proteases, which promotes the dissolution of the surrounding tumor matrix and the basement membrane. The serine protease urokinase-type plasminogen activator(uPA), which is elevated in solid tumors, appears to play a key role in these processes. We used enzymelinked immunoabsorbent assays(ELISA) to test uPA antigen expression in tissue extracts of normal and cancer tissue of 160 gastric cancer patients. uPA level was significantly higher in cancerous tissue than normal gastric tissue(9.4 vs 5.3 ng/mg protein cytosol: p<0.001). When the uPA level was correlated to other prognostic parameters, uPA positivity is associated with grade of anaplasia(p=0.005). Univariate analysis showed that a uPA positivity is significantly associated with short. disease-free survival(p=0.005). Multivariate analysis with known prognostic parameters revealed that the uPA positivity was an independent prognostic parameter for short disease-free survival. These data indicate that uPA is a potentially important prognostic factor in gastric cancer. Consequently, we suggest that modulation of uPA is needed to prevent invasion and metastasis in gastric cancer patients.