To clarify the interrelationship between urokinase-type plasminogen activator receptor (uPAR) and the progression of gastric cancer, uPAR expression in gastric cancer was studied by the reverse transcription (RT)-PCR and immunohistochemistry. uPAR mRNA was expressed in 44 of 46 primary gastric cancers and uPAR immunoreactivity was found in 21 (14%) of 155 tumors. uPAR immunoreactivity was also observed in the fibroblast-like cells and the inflammatory cells including macrophages. The intensity of uPAR immunoreactivity of these cells was weaker than that of cancer cells. uPAR expression detected by RT-PCR may be from cancer cells and/or non-cancerous stromal cells. uPAR immunoreactivity in cancer cells was closely associated with histologic type, nodal status, and macroscopic type. The uPAR positive tumors were closely associated with the macroscopically infiltrating type, undifferentiated type and stage IV disease. Poorly differentiated carcinomas with rich intestitial fibrosis (scirrhous carcinoma) expressed uPAR with a significantly higher incidence than the other histologic types of carcinoma. Growth of scirrhous carcinoma may be a result of a concerted action of the players in the plasminogen activator system, consisting of cancer cells and stromal elements. Furthermore, there was an intimate relationship between the grade of lymph node metastasis and uPAR tissue status. Patients with a uPAR positive tumor had a significantly poorer prognosis than those with uPAR negative tumor. These results indicate that the immunohistochemical diagnosis of uPAR tissue status on the primary tumor of gastric cancer may be a good predictor for the prognosis of patients with gastric cancer.