From a single, chemically-induced rat colonic carcinoma, two subpopulations of tumor cells have been isolated. When injected into syngeneic rats, TR cells give rise to progressive tumors in most of the animals, whereas TS cells give rise to no tumors or to tumors which regress in less than 30 days. TS cells inhibit the growth of TR tumors, whether they are injected before TR cells or simultaneously, at a different site or mixed with the TR cells. Lymph nodes and spleen lymphocytes from animals having rejected TS tumors also inhibit TR-cell growth. On the other hand, TS cells are able to give rise to progressive tumors when they are injected into rats bearing established TR tumors. Lymph nodes and spleen cells of TR tumor-bearing rats are able to enhance TS cell growth. These results suggest that subpopulations of cancer cells contained in the same tumor interact with each other through their effect on the host immune system. The growth of a whole tumor probably depends not only on the growth potential of each constituent subpopulation, but also on the interaction between the subpopulations themselves.