TIF1β, a member of the transcriptional intermediary factor 1 family, has been reported to function as a corepressor for the large class of KRAB domain-containing zinc finger proteins of the Krüppel type. To address the biological function of TIF1β, we have generated TIF1β-deficient mice by gene disruption. TIF1β protein was detected in wild-type but not TIF1β^−/− blastocysts. Homozygous mutant embryos, which developed normally until the blastocyst stage and underwent uterine implantation, were arrested in their development at the early egg-cylinder stage at about embryonic day (E) 5.5 and were completely resorbed by E8.5. Taken together, these results provide genetic evidence that TIF1β is a developmental regulatory protein that exerts function(s) essential for early postimplantation development.