This unit describes two protocols that can be used to quantitate interferon gamma (IFN-gamma), an important modulatory lymphokine that regulates natural, cell-mediated, and humoral immunity by eliciting a number of biological responses in many different cell types. Depending upon the specificity of the reagents used, the assays will detect either human or murine IFN-gamma. The Basic Protocol is an enzyme-linked immunosorbent assay (ELISA) based on IFN-gamma's unique antigenic structure. The Alternate Protocol is a functional activity assay based on IFN-gamma's ability to induce major histocompatibility (MHC) class II antigens (also termed Ia antigens) on responsive cells. The advantage of the ELISA protocol is its specificity, while the advantage of the MHC protocol is its sensitivity.