Alcohol consumption often diminishes antigen-specific cell-mediated immunity. In alcohol-consuming mice IFN-gamma and delayed-type hypersensitivity (DTH) responses are blunted, although antigen-specific T cell proliferation and IL-2 responses are largely unaffected, suggesting that alcohol differentially affects signal transduction pathways. In the present report we explore the use of the phosphatase inhibitor, Na3 VO4 to restore IFN-gamma secretion in the presence of ethanol both in vivo and in vitro. We show that Na3 VO4 restores IFN-gamma in vitro and antigen-specific DTH in vivo to the levels seen in alcohol non-consuming mice. Our data support the contention that ethanol, by up-regulating phosphotyrosine phosphatase, diminishes the IFN-gamma signal transduction pathway.