Developmental stages of Rana esculenta, starting with the posterior limb-bud stage (stage 26) up to a few days after metamorphosis, were examined immunohistochemically to localize cells and fibers producing some POMC-derived peptides, namely, alpha-MSH, ACTH and beta-END. Anti ACTH and anti alpha-MSH revealed a positive reaction in the pars intermedia during all stages of development included in this study, whereas no immunoreactivity in this pituitary zone was ever evidenced with anti beta-END. In the pars distalis strongly positive cells were seen with anti ACTH and anti beta-END, while anti alpha-MSH yielded weakly positive cells. Interestingly, these peptides were colocalized in the same cells. Immunoreactivity for alpha-MSH was no longer present in the pars distalis during metamorphic climax and postmetamorphosis. In the brain of premetamorphic tadpoles, belonging to stages 26 to 30, a few neurons in the posterior telencephalon showed a positive reaction only with anti alpha-MSH, but from stage 31 (prometamorphosis) onwards, ACTH and beta-endorphin-like peptide producing cells, together with alpha-MSH-immunoreactive cells, were seen in this region and in the anterior preoptic area and infundibulum. This situation persisted in the subsequent stages of development. Anti alpha-MSH also revealed weakly positive cells in the olfactory epithelium in premetamorphic tadpoles; strong immunoreactivity with anti alpha-MSH was seen in olfactory epithelium cells in animals during prometamorphosis, metamorphic climax and postmetamorphosis. The possible significance of these findings is briefly discussed.