There is an important need for clinically relevant animal models for human cancers. Toward this goal, histologically intact human colon-cancer specimens derived surgically from patients were implanted orthotopically to the colon or cecum of nude mice. We have observed extensive orthotopic growth in 13 of 20 cases of implanted patient colon tumors. These showed various growth patterns with subsequent regional, lymph-node, and liver metastasis, as well as general abdominal carcinomatosis. Thus, models for human colon cancer have been developed that show (i) local growth, (it) abdominal metastasis, (iiM) general abdominal carcinomatosis with extensive peritoneal seeding, (iv) lymph-node metastasis, (v) liver metastasis, and (vW) colonic obstruction. These models permit the passage of the tumors to form large cohorts. They will facilitate research into the biology of colon cancer metastatic capability and the development of new drugs active against metastatic cancer. These models may also predict the clinical course and the in vivo response to drugs of the cancer of individual patients.There is a need for the development of better animal models for human cancer. Models based on athymic nude mice have been used for this purpose. However, metastatic rates from subcutaneous or intramuscular xenografts have been low or nonexistent even from tumors that were highly metastatic in the patient from whom the tissue was derived (1-5).Recent work from a number of laboratories has indicated that implanting human tumor cells orthotopically in the corresponding organ of nude mice resulted in much higher metastatic rates. For example, a human renal-cell carcinoma obtained from a surgical specimen was dissociated by enzymatic treatment and subcutaneously injected into the renal capsule of nude mice as well as other sites. The injection of human renal-cell carcinoma cells into the kidney ofnude mice produced the highest incidence oftumor establishment and of metastasis to the lungs and other peritoneal organs. The nude-mouse renal capsule appears to be a most advantageous site for implantation of human renal-cell carcinoma (6-8). However, the subrenal capsule may be an advantageous implant site for other tumor types also (9). Human coloncancer cells were dissociated, grown in culture, and subsequently injected into the cecum of nude mice to produce tumors that eventually metastasized to the liver, demonstrating that orthotopic implantation can enhance the metastatic capability of human tumor cells in nude mice (5, 10-13). Similar results also have been achieved for orthotopic implantation of cell lines of human lung cancer (14), human pancreatic cancer (15), bladder cancer (16, 17), melanoma (18, 19), breast cancer (20-22), and head and neck cancer (23). It should be noted, however, that the effects of orthotopicity have not been fully evaluated in that, at least in some cases, metastasis may arise from nonorthotopic sites.Our approach is to avoid disruption of tumor integrity and to orthotopically implant histologically int...