A laboratory study was undertaken to explore the possible interference of phenytoin with the immunosuppressive effect of methylprednisolone sodium succinate on skin graft survival in mice. Full thickness skin allografts were performed on five groups of 10 mice. Each group received various combinations of phenytoin and/or methylprednisolone sodium succinate or no treatment at all (control). In vitro stimulation of lymphocytes from these mice with phytohemagglutinin was carried out to corroborate the immune status of the recipients. All mice demonstrated prolonged graft survival as compared to the control group regardless of what agents were used. Our results indicate that the concomitant administration of phenytoin and methylprednisolone sodium succinate does not accelerate skin homograft rejection in the murine model.