Using MLR, the effect of atorvastatin on proliferation of human and baboon PBMC and human CD4+T cells in response to wild-type (WT) and α1,3-galactosyltransferase gene-knockout (GTKO) porcine aortic endothelial cells (pAEC) was investigated. SLA class-II expression on pAEC before and after 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 20-60-fold, which was downregulated 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 downregulates the primate cellular xenoresponse, possibly through its antiproliferative effect on PBMC and reduction of SLA-II on pAEC.