Portal venous pretransplantation transfusion augments allogeneic skin graft survival in mice transplanted across multiple minor histocompatibility barriers. We have shown in earlier studies that this is correlated with preferential activation for production of type-2 cytokines (interleukin [IL]-4 and IL-10) and decreased production of type-1 cytokines (IL-2 and interferon-gamma). We show that recombinant IL-12, in association with anti-IL-10 monoclonal antibody, can reverse in vivo the graft prolongation afforded by portal venous immunization and the altered cytokine production that follows. These alterations are in turn associated with increased expression of messenger RNA for interferon-gamma, IL-2, and IL-12 and decreased expression of IL-4, IL-10, and IL-13, as determined by non-quantitative polymerase chain reaction using cells obtained from lymph nodes draining the graft. Recombinant IL-12 in vitro also produces dose-related inhibition of activation for production of type-2 cytokines.