To test the hypothesis that interferon-gamma (IFN gamma) and interleukin-1 beta (IL-1 beta) possess antitumor activity on human papillary thyroid carcinoma cells, we studied the in vitro effects of IFN gamma and IL-1 beta on the proliferation and invasiveness of two human PTC cell lines, TPC-1 (TP) and NPA (NP) cells. TP and NP cells were treated with various concentrations of IFN gamma and IL-1 beta alone and in combination. Cell proliferation was assessed by [3H]thymidine incorporation and cell number measurement. Tumor cell invasion was assessed by the ability of cells to penetrate through a Matrigel membrane. Both IFN gamma and IL-1 beta inhibited [3H]thymidine incorporation into TP cells in a dose-dependent manner and decreased TP cell number. In NP cells, treatment with IFN gamma and IL-1 beta also decreased [3H]thymidine incorporation and cell number. The inhibitory effects of IFN gamma and IL-1 beta on tumor cell proliferation were additive in both cell lines. In the invasion experiments, IFN gamma and IL-1 beta reduced the invasiveness of TP and NP cells. Again, the inhibitory effects of IFN gamma and IL-1 beta on tumor cell invasion were additive in both cell lines. In summary, the results showed that both IFN gamma and IL-1 beta are potent inhibitors of the proliferation and invasiveness of TP and NP cells. The additive effects of IFN gamma and IL-1 beta are evidence that they act through different pathways. Our findings suggest that IFN gamma and IL-1 beta are two of the anticancer factors that act to suppress the proliferation and reduce the invasive potential of human papillary thyroid carcinoma cells.