The resting pool of primordial follicles in mammalian ovaries is a potential resource for the genetic manipulation of domestic animals, the preservation of endangered species, and the amelioration of some forms of infertility in humans. Exploitation of this large reservoir of follicles depends on the development of methods for activating primordial follicles to begin growth in vitro and of methods for sustaining follicular growth to the stage at which oocytes are capable of meiotic maturation, fertilization and development to live young. It has been shown that primordial follicles of rodents, cattle and primates can initiate growth in vitro, even in serum-free medium. The signals that cause primordial follicles to leave the resting pool or remain quiescent are unknown. However, of interest is the observation that in cultures of whole rodent ovaries an apparently normal number of follicles leaves the resting pool and begins to grow, whereas in cultures of isolated bovine or primate ovarian cortex almost all primordial follicles activate and develop into primary follicles. This finding suggests that non-cortical portions of the ovary may regulate the flow of follicles from the resting reservoir. In cattle, it has been difficult to sustain follicular growth beyond the primary stage and the development of methods for doing so are critical for achievement of the practical goal of use of the primordial pool for embryo production. However, the development of murine follicles in vitro from the primordial stage through oocyte maturation and fertilization, and the birth of one pup, provides encouragement for efforts to achieve similar results in large mammals.