The tumorigenicity and metastatic behaviour of human colorectal tumors have been assessed in athymic nude mice. Surgical specimens were obtained from colorectal carcinomas or from metastases of different patients. Primary colorectal tumors and their synchronous liver metastases were obtained from three patients. After intramuscular (i.m.) injection into nude mice, tumor cells originating from metastases showed a higher take than those from primary tumors. In general, metastasis-derived tumors had a shorter doubling time than primary-derived tumors. This growth pattern was not associated with the production of spontaneous metastases in nude mice. To investigate the malignant potential of colorectal neoplasms in the nude mouse, tumor cells were injected intravenously (i.v.) (artificial lung metastases) and in the spleen (artificial liver metastases). Colorectal-derived tumor cells produced lung colonies after i.v. injection, but the most dramatic expression of malignancy was the tumor cells' ability to grow in the liver after intrasplenic (i.s.) injection. The ability to grow in the liver of nude mice appeared to be a distinct characteristic of each tumor cell population. Human colorectal tumors were maintained as continuous lines subcutaneously (s.c.) in nude mice. Phenotypic differences, including malignant potential, were generally maintained at different passages. Human colorectal tumors with a definite pattern of malignant behaviour (i.e. to the liver) in the nude mouse provide a unique experimental system for the study of the biology and the therapy of cancer metastases.