&NA;In searching for a suitable animal model system to study colorectal tumor‐cell metastasis, the method of injecting tumor cells directly into the spleen of athymic nude mice was explored. The cells used in this study consisted of the Colo 205 cell line, isolated and established from the ascitic fluid of a patient with adenocarcinoma of the colon. In spite of showing tumorigenicity in nude mice after subcutaneous injections, anchorage‐independent clonal growth in soft agar, and invasion in the chick embryo skin, the Colo 205 cells failed to metastasize to the lung or liver after intrasplenic injections. The effects of interferon, and interferon in combination with 5‐fluorouracil (5‐FU), on tumor formation in the spleen, were studied. The combined interferon‐ and 5‐Fu‐treated animals displayed a significant difference from the controls in the generation of spleen tumors. This combination may possess potentially useful applications in the treatment of solid tumors such as those in the colon and rectum.