Mature mouse oocytes are arrested at metaphase of the second meiotic division. Completion of meiosis and a block to polyspermy is caused by a series of repetitive Ca²⁺ tran-sients triggered by the sperm at fertilization. These Ca²⁺ transients have been widely reported to last for a number of hours but when, or why, they cease is not known. Here we show that Ca²⁺ transients cease during entry into inter-phase, at the time when pronuclei are forming. In fertilized oocytes arrested at metaphase using colcemid, Ca²⁺ tran-sients continued for as long as measurements were made, up to 18 hours after fertilization. Therefore sperm is able to induce Ca²⁺ transients during metaphase but not during interphase. In addition metaphase II oocytes, but not pronuclear stage 1-cell embryos showed highly repetitive Ca²⁺ oscillations in response to microinjection of inositol trisphosphate. This was explored further by treating in vitro maturing oocytes at metaphase I for 4-5 hours with cycloheximide, which induced nuclear progression to inter-phase (nucleus formation) and subsequent re-entry to metaphase (nuclear envelope breakdown). Fertilization of cycloheximide-treated oocytes revealed that continuous Ca²⁺ oscillations in response to sperm were observed after nuclear envelope breakdown but not during interphase. However interphase oocytes were able to generate Ca²⁺ transients in response to thimerosal. This data suggests that the ability of the sperm to trigger repetitive Ca²⁺ transients in oocytes is modulated in a cell cycle-dependent manner.