Cytokine gene therapy for cancer could involve either the direct delivery of cytokine genes to established tumours to stimulate their rejection or the injection of cytokine-secreting tumour cells to stimulate an immune response that could reduce metastatic disease. To assess the feasibility of the first approach, we have compared the ability of different cytokine-secreting tumour cells to induce the rejection of admixed, unmodified cells. While interleukin (IL)-2- or interleukin-4-secreting tumour cells were ineffective, interferon-gamma (IFN-gamma)-secreting cells could induce rejection of 10% admixed, unmodified cells. Because direct gene delivery to tumours is unlikely to be 100% efficient, these data suggest that IFN-gamma may be the most suitable of these cytokines for this approach. However, we have demonstrated that injection of IL-2-secreting tumour cells, following primary tumour excision, can prevent the development of metastases and prolong survival of rats. This suggests that IL-2-secreting tumour cells can be effective in the treatment of metastatic disease.