In Xenopus, it has been shown that semi-xenogeneic adult skin grafts usually render donor-specific tolerance to perimetamorphic larvae, while these skin grafts are never accepted in adults. The mechanisms operating in this tolerance induction are largely unclear. The present investigation was planned to test whether lower responsiveness of larvae to non-self antigens could be ascribable to perimetamorphic tolerance induction. We tried to induce tolerance in adults by treating them with Cyclosporin A (CsA), which is known to decline the immune system in mammals. The results showed that CsA-treated adults could never be rendered tolerant to semi-xenogeneic skin grafts, although the grafts were not rejected as long as the treatment was continued. We have also proposed a possibly different mechanisms for the rejection of semi-xenogeneic skin grafts and of full-xenogeneic skin grafts.