It has been shown that tumour necrosis factor-alpha (TNF-alpha) induces the gene expression of collagenase and enhances the invasiveness of many cell types. However, we have previously demonstrated that interferon-gamma (IFN-gamma) induces the chemotactic response of cells and we have studied the in vitro effects of both cytokines on invasive migration using a human fibrosarcoma cell line (HT-1080). Invasive migration occurred with HT-1800 cells through a basement membrane equivalent (matrigel) and collagen type I gel. Pre-incubation of cells with increasing concentrations of IFN-gamma resulted in a dose-dependent reduction of this invasive migration. TNF-alpha considerably enhanced the invasiveness of HT-1080 cells and of fibroblasts. This effect could be significantly diminished by the pre-incubation of cells with IFN-gamma. Inhibition of invasiveness did not appear to be due to an altered binding to the barriers or altered collagenolytic activity of these cells, as shown by attachment and collagenase assays. These data support the concept that IFN-gamma can reduce the invasiveness of transformed cells which contributes to its in vivo anti-neoplastic effect.