Malignant tumors contrast with benign ones in their ability to invade adjacent tissue and to metastasize. The urokinase plasminogen activator is a proteolytic enzyme that can facilitate these processes. In many carcinomas, the concentration of the urokinase plasminogen activator system is high. The high expression of these enzymes is related to tumor grade. In this study, we have investigated whether secretion of the urokinase plasminogen activator, urokinase plasminogen activator receptor, and plasminogen activator inhibitor 1 in normal kidney tissue and kidney cancer tissue follows this pattern. We have found that urokinase plasminogen activator, urokinase plasminogen activator receptor, and plasminogen activator inhibitor 1 were expressed in higher levels in kidney cancers (squamous cell carcinoma and renal cell carcinoma) than in normal kidney tissue and that these differences were statistically significant (P < or = 0.05). In renal cell carcinomas, we have observed differences between normal kidney tissue and renal cell carcinomas in males and Caucasians but not in females and African Americans (P < or = 0.05). Expression of the urokinase plasminogen activator system was also higher in grade III tumors when compared with lower-grade tumors or normal tissue.