In order to adapt to a different habitat, under the influence of thyroid hormones, amphibian skin undergoes morphological, biochemical and physiological changes and the tail completely regresses during metamorphosis. Body epidermis remains non‐keratinized throughout the larval life and keratinizes during metamorphosis, resulting in adult frogs with a cornified epidermal cells covering the body. The significance of nitric oxide (NO) in many biological processes is well known. Signaling mediated by nitric oxide can contribute to stress‐related responses where these molecules can act as regulators of metamorphic transitions. However, there is scanty information on how NO acts as a signaling molecule during cell death and differentiation in amphibian tissues. Presently, we investigated the role of nitric oxide synthase (NOS) in skin and tail using Western blot analysis and immunohistochemistry during metamorphosis of tadpoles, Xenopus laevis . Our results indicate involvement of only neuronal NOS (NOS I) in skin whereas in tail inducible NOS (NOS II) is also present. In skin, neuronal NOS is present during the functional maturation phase during metamorphosis. In contrast, in tail both NOS I and II are found to be present before the beginning of tail regression. Implications of these findings are discussed in terms of putative functional importance of differential isoform expression in the context of developmental processes in this system. This research was supported by William Paterson University.