Previous studies from our laboratory show that ethanol consumption impairs antigen-specific, cell-mediated, but not, humoral immune responses of C57BL/6, BALB/c, and D011.10 T-cell receptor transgenic mice. This ethanol-associated deficit is associated with decreased interleukin (IL)-12 and interferon–γ (IFN-γ) production, but not IL-2 or antigen-specific T-cell proliferation by explanted leukocytes from ethanol-consuming mice. IL-12 expression by macrophage/monocytes is viewed as a requirement for the production of IFN-γ by Th1 lymphocytes that mediate cellular immunity. In this study, we restored antigen-specific, cell-mediated immunity, delayed hypersensitivity, to ethanol-consuming C57BL/6 or BALB/c mice with a single 100 ng of intravenous injection of recombinant IL-12 at the time of immunization. The addition of exogenous recombinant IL-12 to co-cultures of antigen-presenting cells derived from ethanol-consuming mice and purified T cells derived from ethanol-nonconsuming DO11.10 repairs the ability of Th1 cells to make IFN-γ in response to antigen. Administration of recombinant IL-12 opens a potential for restoring cell-mediated immune function to ethanol-consuming individuals.