Tumour cell motility and attachment are crucial requirements in the formation of metastatic lesions. These properties are affected by a number of cytokines including hepatocyte growth factor/scatter factor (HGF/SF) and several immunoregulatory proteins, including interleukin-12 (IL-12). Although IL-12 has been reported to exhibit potent anti-tumour effects in vivo, a direct effect of IL-12 on cancer cells has not been reported. We show here that IL-12 directly inhibited the attachment of the human colon cancer cell lines HRT18, HT29 and HT115 to Matrigel, HGF/SF-stimulated cell motility and HGF/SF-induced cell invasion through a reconstituted basement membrane. IL-12 did not affect the growth of these cell lines. Flow cytometry, Western analysis and immunohistochemistry revealed an up-regulation of E-cadherin cell-surface adhesion molecules. These direct effects of IL-12 on colon cancer cells suggest a potentially important role for IL-12 in metastasis.