Nuclear transplantation was developed 50 years ago in frogs to test whether nuclei from differentiated cells remain genetically equivalent to zygotic nuclei. Results from cloning experiments in frogs and mice indicate that nuclei gradually lose potency during development from embryonic to adult cells. However, even though adult mature lymphocytes were recently shown to remain genetically totipotent, no evidence exists to show that surviving clones originate from the nuclei of terminally differentiated cells. Thus, it is equally possible that many cloned animals are in fact derived from the nuclei of less differentiated adult cells such as adult stem cells. These cells might be more easily reprogrammed than terminally differentiated cells and may support development of a clone at a higher efficiency. Importantly, irrespective of the donor cell, clones display common abnormalities such as foetal and placental overgrowth. Indeed, gene expression analyses and extensive phenotypic characterisation of cloned animals suggest that most, if not all, clones suffer from at least subtle abnormalities.