Development of a fertilizable oocyte is a complex process that relies on the precise temporal and spatial expression of specific genes in germ cells and in surrounding somatic cells. Since female mice null for Taf4b, a TBP associated factor, are sterile, we sought to determine when during follicular development this phenotype was first observed. At postnatal day 3, ovaries of Taf4b null females contained fewer (P < 0.01) oocytes than ovaries of wild type and heterozygous Taf4b mice. However, expression of only one somatic cell marker Foxl2 was reduced in ovaries at day 15. Despite the reduced number of follicles, many proceed to the antral stage, multiple genes associated with granulosa cell differentiation and oocyte maturation were expressed in a normal pattern, and immature Taf4b null females could be hormonally primed to ovulate and mate. However, the ovulated cumulus oocyte complexes from the Taf4b null mice had fewer (P < 0.01) cumulus cells, and the oocytes were functionally abnormal. GVBD and polar body extrusion were reduced significantly (P < 0.01). The few oocytes that were fertilized failed to progress beyond the two-cell stage of development. Thus, infertility in Taf4b null female mice is associated with defects in early follicle formation, oocyte maturation, and zygotic cleavage following ovulation and fertilization.