Using mixed lymphocyte reaction (MLR), the effect of atorvastatin on proliferation of human and baboon peripheral blood mononuclear cells (PBMCs) and human CD4 T cells in response to wild-type (WT) and α-1,3- galactosyltransferase gene-knockout (GTKO) porcine aortic endothelial cells (pAECs) was investigated. swine leukocyte antigen class-II (SLA II) expression on pAEC before and after porcine interferon gamma (pIFN-γ) stimulation, and the effect of atorvastatin on this expression was assessed. Added to the MLR, atorvastatin reduced (i) the human PBMC response to unstimulated (P<0.05) and (ii) the human and baboon PBMC responses to stimulated (P<0.05) WT and GTKO pAEC. Atorvastatin treatment of human PBMC before MLR reduced their response to stimulated WT (P<0.05) and GTKO (P<0.05) pAEC. Stimulation of pAEC with pIFN-γ increased SLA II expression 20- to 60-fold, which was down-regulated by atorvastatin. Atorvastatin treatment of stimulated pAEC before MLR reduced proliferation of human PBMC (P<0.05) and CD4 T cells (P<0.05). Atorvastatin down-regulates the primate cellular xenoresponse, possibly through its antiproliferative effect on PBMCs and the reduction of SLA II on pAECs.