More than 12 years since the first animal was cloned from an adult somatic cell, many somatic cell nuclei still have to be transferred into enucleated meiosis II (MII) oocytes to produce even one offspring. In part, this is because the best way to remove the acetyl and methyl groups added to the chromatin of somatic cells during development, and thus return them to a pluripotent state, is unknown. On p. 3935, however, Bui and colleagues claim that `genomic reprogramming' factors in the cytoplasm of mouse oocytes at the germinal vesicle (GV) stage of maturation could improve cloning efficiency. The researchers show that GV oocyte cytoplasm (but not MII oocyte cytoplasm) completely demethylates histone H3 at lysine 9 in somatic nuclei. Furthermore, exposing somatic nuclei to cytoplasmic lysates of GV oocytes before their microinjection into MII oocytes promotes the production of cloned offspring. The as yet unidentified genomic reprogramming factors in GV oocyte cytoplasm may, therefore, have the potential to improve the efficiency of reproductive cloning.