A fertilization-induced increase in intracellular Ca²⁺is responsible for initiating all of the events of egg activation. In mammals, the Ca²⁺increase takes the form of a series of Ca²⁺oscillations showing complex temporal and spatial properties. To understand the nature of these changes, we have investigated the expression patterns of the three isoforms of the inositol trisphosphate receptor (InsP₃R) during oocyte maturation and preimplantation development. We find that mouse oocytes express mRNAs for all three InsP₃R subtypes. Semiquantitative ratio reverse-transcriptase polymerase chain reaction shows that the type II isoform is the predominant message in mature oocytes, representing 67% of the InsP₃R mRNA. In contrast, protein analysis reveals that the type I isoform accounts for all of the detectable InsP₃R protein, despite representing only 20% of the InsP₃R mRNA. The levels of InsP₃R protein were examined to determine whether they correlated with the Ca²⁺signaling events surrounding the fertilization process. Type I InsP₃R protein increased during oocyte maturation and, in addition, within 8 h of fertilization underwent a dramatic decrease. During development to the blastocyst the level of type I InsP₃R protein did not return to prefertilization levels and types II and III remained below our detection limit. The decrease in InsP₃R protein after fertilization was found to correlate with a decrease in the sensitivity of InsP₃-induced Ca²⁺release. These studies show that the expression of InsP₃R mRNA is developmentally regulated, that Ca²⁺signaling at fertilization is mediated exclusively through the type I InsP₃R, and that the InsP₃R is downregulated after fertilization.