At fertilization, the release of intracellular calcium is necessary and suf
ficient for most, if not virtually all, of the major events of egg activati
on that are responsible for the onset of embryonic development. In mammalia
n eggs, repetitive calcium oscillations stimulate egg activation events thr
ough calcium-dependent effectors, such as calmodulin, protein kinases, and
specific proteins involved in exocytosis. One of the earliest calcium-depen
dent events is the exocytosis of cortical granules (CGs), a secretory event
resulting in the block to polyspermy and the prevention of triploidy. Emer
ging studies suggest that CG release in mature eggs is dependent upon calci
um-dependent proteins similar to those in somatic cells employed to undergo
calcium-regulated exocytosis. In contrast, pre-ovulatory oocytes are incom
petent to undergo CG exocytosis due to deficiencies in the ability to relea
se and respond to increases in intracellular calcium. The development of co
mpetence to release and respond to calcium is relevant to both animal and h
uman in vitro fertilization programs that largely utilize ovarian oocytes n
ot all of which are fully activation competent.