Cross-species somatic all number transfer (SCNT) provides a potential solution to overcome the problem of oocyte shortage for therapeutic cloning. To further characterize the system, we constructed cytoplasm hybrid embryos between bovine oocytes and human fibroblasts and examined dynamics of human gene activation during preimplantation stages. Data from this study showed that human embryonic genes, OCT4, SOX2, NANOG, E-CADHERIN, as well as beta-ACTIN, were activated by enucleated bovine oocytes. Activation of human genes was correlated with developmental potential of the embryos. The extent of human gene activation varied drastically and was incomplete in a large proportion of the embryos. Activation of human genes in the human-bovine cytoplasm hybrid embryos occurs in a temporal pattern resembling that of the bovine species. Results from this study suggest that human gene products are required for hybrid embryos to develop to later preimplantation stages. Facilitating human genome activation may improve successful rates in cross-species SCNT.