The effects of splenectomy on tumor growth following inoculation with a relatively large number of cells (1 X 10(7) ) and a smaller number of cells (5 X 10(5) ) of Meth I tumor were studied. When 1 X 10(7) tumor cells were inoculated, tumor growth in splenectomized mice was depressed, while tumor in sham-operated mice grew progressively. On the contrary, when 5 X 10(5) tumor cells were inoculated, the tumor take was lower in sham-operated than in splenectomized mice. The spleen cells from mice inoculated with either a large or small number of tumor cells, showed an equally potent cytotoxic activity, but no detectable suppressor cell activity. On the other hand, the activity of immunosuppressive factor was detected in sera from mice inoculated with 1 X 10(7) tumor cells, but not in those given 5 X 10(5) cells. The effect of splenectomy on tumor growth is, thus, bidirectional, depending on the dose of tumor cells inoculated.