This paper focuses on the relationship between the developmental programs that regulate nuclear and cytoplasmic maturation of mouse oocytes. As oocytes near completion of their growth phase, they become competent to resume meiosis when isolated from the small antral follicles and cultured, but the progression of meiosis in many of these oocytes stops at metaphase I (MI). With further growth and development at the germinal vesicle (GV) stage, however, these oocytes become competent to complete nuclear maturation and progress to metaphase II (MII). In this study, about 44% of the oocytes were arrested at MI after isolation from the small antral follicles of 18-day-old mice and culture for 16 to 17 hr. Upon insemination, these MI-arrested oocytes produced the first polar body, formed pronuclei, cleaved, and developed to the blastocyst stage. Seventy five percent of these blastocysts were triploid, the remainder were diploid. Treatment of MI-arrested oocytes with calcium ionophore resulted in the completion of the first meiotic division and parthenogenetic activation. Moreover, while the pattern of proteins synthesized in MI-arrested oocytes was quite different from that of normal MI oocytes as determined by [35S]methionine labeling and two-dimensional gel electrophoresis, it was similar to that of MII-arrested oocytes. It was therefore concluded that some critical aspects of cytoplasmic maturation can occur in oocytes whose nuclear maturation is arrested at MI. In addition, triggers that promote entry of MII-arrested oocytes into anaphase II are sufficient to drive MI-arrested oocytes into anaphase I and to produce the first polar body when the triggers are generated in mature cytoplasm. The developmental capacity of MII oocytes that matured in vitro after isolation from 18- or 26-day-old mice were compared. The frequency of fertilization and cleavage to the 2-cell stage was equal in both groups. In surprising contrast, the ability to complete the 2-cell stage to blastocyst transition occurred much more frequently when the oocytes were from the 26- than the 18-day-old mice (82 and 27%, respectively). Thus, even though both groups of oocytes had completed nuclear maturation by progressing to MII, oocytes from the smaller follicles of the younger mice were deficient in maternal factors essential for development of embryos beyond the 2-cell stage. Further differentiation of these GV-stage oocytes of small antral follicles is therefore required to produce eggs competent of completing preimplantation development.