The mesenchyme of the anuran tadpole has been known to induce the regional specificity of epidermis which is expressed during metamorphosis as a body (head and trunk)-or a tail-specific change: the former epidermis transforms into the adult-type, while the latter commits programmed cell death. The inductive activity of the mesenchyme was characterized in relation to both its premetamorphic structural change and the action of thyroid hormone (TH). The epidermis and the mesenchyme were obtained from the body and the tail of tadpoles of the bullfrog Rana catesbeiana at stages IV or X defined by Taylor and Kollros (1946), recombined heterotypically, and were autografted to see the mesenchymal effect on the characteristics of the epidermis. The mesenchyme at stage IV showed inductive activity toward the epidermis and changed its inherent characteristics, while the mesencheme at stage X lost it. The skin at stage IV showed uniformity in its structure over the entire surface of the animal. The histology of stage X skin was region-dependent. The connective tissue was newly developed between the skin basement membrane and thick collagen lamella in the body but not in the tail. A trace of TH was suggested to be involved in inducing these mesenchymal changes, because the treatment of tadpoles at stage IV with thiourea inhibited the appearance of new connective tissue. A three-step mechanism in the metamorphic changes of the tadpole skin is proposed: (1) TH-independent early premetamorphic induction; (2) premetamorphic remodeling induced by a trace of TH; and (3) metamorphic remodeling triggered by a high dose of TH.