Interferon gamma (IFN-gamma) plays an important role in immune response, apoptosis, and anti-tumor activity. Its biological activity depends on expression of IFN-gamma receptor (IFN-gammaR). To address whether increased expression of IFN-gammaR is associated in vivo with a higher biological response by IFN-gamma, we constructed an adenovirus vector including murine IFN-gammaR (Ad-mIFN-gammaR). We confirmed the appropriate function of mIFN-gammaR derived from Ad-mIFN-gammaR based on the observation of signal transduction and transcription. We also found that elevated expression of mIFN-gammaR increases sensitivity to recombinant murine IFN-gamma (rmlFN-gamma) in vitro in target cells. Furthermore, we demonstrated that the growth rate of tumors transfected with Ad-mIFN-gammaR is suppressed in response to rmIFN-gamma in vitro and that such growth suppression is partly due to apoptosis. To our knowledge, this is the first report of adenovirus-mediated IFN-gammaR gene transfer being effective in augmenting the biological activity of IFN-gamma, and the strategy employed in the present study will be useful in studying other kinds of cytokine receptors and applications to gene therapy for cancer and infectious diseases. (C) 2002 Elsevier Science (USA).