These studies describe the effects of recombinant human (rHu) and recombinant murine (rMu) interleukin 12 (IL-12) in the porcine system. To examine the effects of rHu and rMu IL-12, porcine PBL were cultured with rHu and rMu IL-12, and then used for a NK assay. Significant enhancement of porcine NK cell cytotoxicity was observed, and maximal enhancement was reached after 26 hr culture in nanogram quantities (5 ng/ml = 10 units/ml) of rHu and rMu IL-12. Monoclonal antibody (mAb) specific for human IL-12, C8.6, blocked rHu IL-12 enhanced porcine natural killer (NK) cytotoxicity. It was also shown that rHu IL-12 had additive effects on enhancement of NK cell cytotoxicity with PNK-E/G7 mAbs which react with cytolytic trigger molecules on porcine NK cells. By using purified NK cells, porcine tumor necrosis factor-alpha (TNF-alpha) secretion was measured on rHu IL-12 and PNK-E/G7 mAb-activated NK cells. rHu IL-12 and PNK-E/G7 mAbs synergize to induce TNF-alpha secretion. These data indicate that rHu and rMu IL-12 are cross-reactive in the porcine system and suggest the potential use of the porcine system as an important animal model for further study of rHu IL-12.