Larval as well as adult frogs (Xenopus laevis) are immunocompetent. Yet, whereas adults will vigorously reject MHC-incompatible skin grafts, metamorphosing larvae may not. Previous studies have revealed that this graft survival reflects an immunologically specific host tolerance. The role of the thymus in the acquisition of this tolerance to MHC-disparate skin allografts by metamorphosing outbred and inbred frogs has been investigated. When thymectomy was performed during midlarval or late larval life, it markedly impaired tolerance, as judged by an increased frequency of hosts rejecting grafts and by a curtailed survival time of rejected transplants. The efficacy with which thymectomy affected tolerance in this way was dependent on the developmental stage at which it was performed, on the haplotype disparity between donor and host, and on the size of the transplant. These last two variables also affect tolerance in intact perimetamorphic animals. Thymectomy during larval life affected the survival of grafts transplanted during postmetamorphic life. This influence was also dependent on the particular MHC haplotype incompatibility involved, and on the size of the transplant.