Previously, we have demonstrated that IFN-alpha synergizes with IL-2 in the augmentation of lymphokine activated killer (LAK) cells in various compartments of mice. Both proliferation and augmentation of LAK cell activity on a per cell basis was observed in response to IFN-alpha and IL-2 therapy. These observations suggest that anti-tumor effects of IFN-alpha with IL-2 may be mediated through activation of LAK cells. The administration of IFN-gamma with IL-2 increased LAK activity while it has not been shown to cause synergistic anti-tumor effects. Other effectors such as CTL, macrophages and unknown cell population may be responsible for differences observed with the two interferons. Additionally, we have observed that IL-6 causes the proliferation of lymphoid cells in the spleen of mice. These cells appear to be T lymphocytes because no proliferation was observed in the irradiated and nude mice. Proliferating cells did not bear NK or LAK activity, however, secondary CTL activity was induced by IL-6.