The objectives of this program are to improve the local control of hepatic metastasis of colorectal carcinoma through intra-arterial or portal vein chemotherapy. Clinical and laboratory studies are integrated so that leads in the laboratory are followed up by clinical studies and vice versa. memorial Sloan-Kettering Cancer Center has a sufficient number of patients (approximately 125/year) who either have surgical resection of metastatic colorectal cancer in the liver or hepatic artery catheters/implantable pump placed, to allow these clinical studies to be done in a single institution. The program includes Phase II and III studies of therapy (Project IA); improved techniques for quantitating response (Project IB); laboratory studies to assess natural and acquired resistance to fluorodeoxyuridine and dichloromethotrexate (Project II); and a rat model system for assessing toxicity and response to chemotherapeutic agents and protective agents (Project III). Investigators participating in this project are from the disciplines of medical oncology, surgery, radiation therapy, radiology, radiation physics, developmental therapy and biostatistics.