We have studied the metastatic behavior of five human colon tumor cell lines (LS174T, WiDr, Caco-2, SW 620 and SW 480) using intrasplenic-nude mouse (ISMS) and intravenous-nude mouse (IVMS) model systems. LS174T was highly metastatic in both systems. In the IVMS system, LS174T cells produced lung metastasis and also grew in the skin as if the cells had been injected subcutaneously. We have also studied the anti-metastatic activity of three anticancer drugs (5-fluorouracil (5-FU), doxorubicin (DX) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) using LS174T cells and both ISMS and IVMS systems. The drugs were given intravenously on day 19 and 26 of tumor cell injection. Mice were sacrificed and organs observed for metastatic growth 4-6 weeks after cell injection. The results show that in the ISMS system, BCNU and 5-FU are inactive against both the liver metastasis and primary growth in the spleen. DX inhibits metastatic growth but not the primary growth. In the IVMS system, BCNU is inactive, whereas 5-FU and DX are active against the metastatic growth. Thus, DX may have activity against blood-borne human colon tumor metastasis.