Jak2, which is a member of the Janus tyrosine kinase family, plays essential roles in cytokine signal transduction and in the regulation of cell growth and gene expression. To investigate the involvement of Jak2 in the regulation of early preimplantation development, we examined the expression of Jak2 in mouse embryos. Reverse transcription-polymerase chain reaction assays revealed that the relative amount of Jak2 mRNA was highest in unfertilized oocytes, gradually decreased until the four-cell stage, and remained at low levels until the blastocyst stage. Immunocytochemistry showed that Jak2 was localized predominantly to the female pronucleus in one-cell embryos. The immunofluorescence signal was very weak or undetectable in the male pronucleus. In unfertilized oocytes and one-cell embryos at M phase, Jak2 was localized to the chromosomes. After cleavage to the two-cell stage, the intensity of the immunofluorescence signal decreased in the nucleus while the embryos were in late G2. This decrease was independent of DNA synthesis because it was not affected by inhibition of DNA replication. However, inhibition of protein synthesis repressed the disappearance of Jak2 from the nucleus. These results suggest a novel function for Jak2 in the regulation of early preimplantation development.