The calcium ([Ca²⁺]_i) oscillations associated with mammalian fertilization and required to induce egg activation occur during M-phase stages of the cell cycle. The molecular mechanisms underlying this regulation remain unproven and may be multi-layered. Type 1 inositol 1,4,5-trisphosphate receptors (IP₃R-1), which mediate [Ca²⁺]_i release during fertilization, have emerged as key regulatory units because they contain multiple phosphorylation consensus sites and undergo changes in cellular location and mass prior to and following fertilization. Hence, control of IP₃R-1 function together with regulation of PLCζ activity, the putative sperm factor, may combine to impart cell cycle and species-specific [Ca²⁺]_i oscillations characteristic of mammalian fertilization.