Metastasis is the most important factor for prognosis in cancer patients, and its occurrence is largely associated with host immune response. We found that the presence of a growing tumor of colon 26, a mouse colon cancer cell line, completely inhibited lung colony formation in a mouse injected with colon 26 intravenously, whereas depletion of effector cells, such as natural killer and T cell subsets, did not affect antimetastasis of colon 26. Since colon 26 releases large amounts of interleukin-6 (IL-6) spontaneously, we studied the association of IL-6 with lung metastasis. Serum IL-6 level increased gradually and reached 12.6 pg/ml five days after inoculation of colon 26 in the back of mice, while at the same time, lung colony formation was inhibited. Moreover, expression of IL-6 mRNA in lung was observed to be associated with elevated serum IL-6 level. We show the first evidence that inhibition of lung metastases in tumor-bearing mice by colon 26 is closely associated with an increase in serum IL-6, but not in cellular immunity.