IFN-gamma is a T-cell derived lymphokine which possesses antitumoral activity for a variety of malignant cells by virtue of its direct effect on cell growth and by its immunomodulatory activity. All IFN-gamma actions are initiated by binding to high affinity cell surface receptors, which are constitutively expressed in virtually all cell lines from various tissues. Although the detailed structure of the IFN-gamma receptor is still elusive, the available data suggest that the high affinity IFN-gamma binding site is a heterodimeric molecule of 128 kDa comprised of two subunits of 53 and 75 kDa, which is invariantly expressed in distinct tumor cells, differing in their response to IFN-gamma. Thus, the capability and type of cellular response to IFN-gamma appears to be largely determined at a post-receptor level. Nevertheless, in sensitive cell lines, the magnitude of response is proportional to the quantity of receptor ligand interactions. This could be important for the definition of effective doses in clinical applications of IFN-gamma, as distinct tumor cells are heterogeneous with respect to quantity of IFN-gamma receptors, with greater 20-fold differences of the number of receptors per cell.