Metastatic spread of tumor cells depends upon intravasation of malignant cells from the primary site and extravasation into the distant organs following remodeling of the basement membrane. We have investigated the metastatic potential of five tumorigenic human colon carcinoma cell lines, LS 174T, SW 620, WiDr, SW 480 and Caco-2 using intrasplenic injection in nude mice. LS 174T is most aggressive causing liver metastasis in all animals within 6 weeks. SW 620 and WiDr produced liver metastasis in 70% and 30% of the animals but after a period of 12 weeks whereas SW 480 and Caco-2 were not metastatic. LS 174T exhibited high cell-associated urokinase-type plasminogen activator (u-PA) and high secreted u-PA and tissue plasminogen activator (t-PA) levels. WiDr, SW 480 and Caco-2 had essentially similar low levels of cell associated u-PA but WiDr had higher secreted u-PA levels as comprated to the SW 480 and Caco-2 cells. The level of secreted MMP-2 (72 kDa gelatinase) was highest in the most metastatic cell line, LS 174T, and lower in other less metastatic ones. These data show that metastatic behavior of human colon tumor cells correlates with the enhanced secretion of plasminogen activators and MMP-2 by these cells.