The rat is a reference animal model for physiological studies and for the analysis of multigenic human diseases such as hypertension, diabetes, and neurological disorders (1). Genetic manipulation in the rat is hampered by the lack of suitable technologies such as embryonic stem cells (ES), which are routinely used to generate targeted mutations in the mouse. Cloning through somatic cell nuclear transfer (SCNT) is a potential alternative approach in species for which ES technologies are unavailable. However, all previous efforts to clone rats have been unsuccessful, with developmental arrest at implantation stage [(2) and references therein]. The fine-tuned coordination between nuclear transfer and timing of oocyte activation is critical to the outcome of somatic cloning. This coordination is hampered in the rat because almost all the oocytes spontaneously, although abortively, activate within 60 min of their removal from oviducts (3). Such rapid but incomplete activation process is not encountered in other cloned species. To allow embryo reconstruction before the onset of oocyte activation, we initially developed a one-step SCNT procedure for the rapid substitution of the endogenous meiotic metaphase nucleus by an exogenous mitotic one. This latter nucleus was isolated from synchronized cultured fetal CD–Sprague Dawley fibroblasts [12.5 days post coitum (dpc)]. Individual mitotic nuclei were injected into a recipient OFA–Sprague Dawley oocyte, from which the meiotic metaphase nucleus was withdrawn while removing the micropipette from cytoplasm after injection. However, within 30 min after recovery, 70% of oocytes showed clear morphological evidence of spontaneous release from the second meiotic metaphase arrest (oocyte metaphase MII)(Fig. 1A). When activation of cloned embryos (Fig. 1B) was induced and maintained by exposure (2 hours) to a cdc2-specific kinase inhibitor (butyrolactone, 150 μM)(4), 201 of 221 reconstructed embryos expelled the polar body and subsequently divided into two-cell embryos. Their transfer into OFA–Sprague Dawley foster mothers (11 recipients, 221 embryos) resulted in nine implantation sites but no fetal development.