We investigated the effects of IL-2 and IFN-gamma on the expression of the proto-oncogene c-fms mRNA, which encodes for the macrophage CSF receptor. Low constitutive expression of c-fms mRNA was detected in fresh human monocytes. Stimulation of monocytes with IL-2 induced a significant increase in c-fms mRNA relative to medium control that was observed as early as 6 h after IL-2 stimulation. Dose-response experiments showed that 100 U/ml of IL-2 were sufficient to enhance the expression of c-fms mRNA. In contrast, IFN-gamma did not modify the levels of c-fms transcript. Immunoprecipitation experiments demonstrated that IL-2 enhanced c-fms glycoprotein levels. Experiments in which monocytes were activated with IFN-gamma or IL-2 followed by macrophage CSF-1 and then tested for tumoricidal activity demonstrated that macrophage CSF-1 sustained the cytotoxic activity induced by IL-2 but not by IFN-gamma. These data demonstrate that IL-2 enhances c-fms mRNA and c-fms glycoprotein expression suggesting that IL-2, by augmenting expression of macrophage CSF-1 receptors, can lead to prolongation of monocyte-mediated tumoricidal activity obtained in the presence of exogenous macrophage CSF-1.