A fertilization-induced increase in intracellular Ca 2+ is responsible for initiating all of the events of egg activation. In mammals, the Ca 2+ increase takes the form of a series of Ca 2+ 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 (InsP 3 R) during oocyte maturation and preimplantation development. We find that mouse oocytes express mRNAs for all three InsP 3 R subtypes. Semiquantitative ratio reverse-transcriptase polymerase chain reaction shown that the type II isoform is the predominant message in mature oocytes, representing 67% of the InsP 3 R mRNA. In contrast, protein analysis reveals that the type isoform accounts for all of the detectable InsP 3 R protein, despite representing only 20% of the InsP 3 R mRNA. The levels of InsP 3 R protein were examined to determine whether they correlated with the Ca 2+ signaling events surrounding the fertilization process. Type I InsP 3 R 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 InsP 3 R protein did not return to prefertilization levels and types II and III remained below our detection limit. The decrease in InsP 3 R protein after fertilization was found to correlate with a decrease in the sensitivity of InsP 3 -induced Ca 2+ release. These studies show that the expression of InsP 3 R mRNA is developmentally regulated, that Ca 2+ signaling at fertilization is mediated exclusively through the type I InsP 3 R, and that the InsP 3 R is downregulated after fertilization.