Self-renewing, totipotent embryonic stem (ES) cells may provide a virtually unlimited donor source for transplantation and tissue generation in vitro. Mouse ES cell-derived hematopoietic precursors, cardiomyocytes, neural precursors, or insulin-producing cells have been successful transplanted into recipient animals. Since human ES cells (and embyronic germ cells) were recently isolated and shown to have a similar potential for differentiation to mouse ES cells, ES-derived cells may be applied, in the near future, to patients with various diseases. Ultimately, in vitro-generated tissues from human ES cells may take the place, at least in part, or organ transplantation. ES-derived tissue specific cells may also be an ideal source for drug efficacy and toxicity testing. The promise of ES cell research is, however, tempered by the strong ethnical concerns regarding the use of fertilized human eggs to establish ES cells. In particular, in order to prepare human ES cells for large numbers of the histocompatibility types in population, there would be the necessity for a great increase in the use of human eggs. Here we attempt to generate pluripotent ES-like cells by fusion of adult somatic cells and the cytoplasts prepared from mouse ES cells. In our preliminary experiments, we have successfully generated pluripotent stem cells by ES cell-somatic cell fusion. Moreover, recent success in mammalian cloning indicates that the cytoplasm of fertilized eggs is sufficient to reprogram the somatic nuclei. The cytoplasm of ES cells may retain the ability to reprogram somatic nuclei as well. If the method could be applied to the human system, autologous pluripotent stem cells could be prepared for any individual using the one human ES line that has already been established. Pluripotent ES-like stem cells with the genotype of somatic cells could then be utilized for autologous cell replacement therapy and personal drug efficacy/toxicity test, inc combination with the in vitro differentiation techniques. In addition to such clinical significance, the current study could provide the basis for an improved system to explore the mechanisms underlying nuclear reprogramming.