Inhibition of urokinase plasminogen activator (uPA) has been shown to suppress cancer cell invasion and metastasis in the laboratory setting by numerous investigators. Most studies have used murine cell lines implanted in syngeneic rodents or transfected human cell lines grown in immunocompromised laboratory hosts. In this study using Matrigel invasion chambers and two separate uPA inhibitors, amiloride and B428, the invasive capacity of unaltered human breast cancer cells was significantly suppressed. Cell proliferation was also suppressed to a lesser degree. These findings suggest that uPA inhibition may be a valid clinical approach to the control of the invasion and metastasis of human cancers.