The release of intracellular calcium (Ca²⁺) via either inositol 1,4,5-trisphosphate receptors (IP3R) or ryanodine receptors (RyR) activates a wide variety of signaling pathways in virtually every type of cell. In the present study we demonstrate that at early stages of development IP3R mRNA and functional IP3-gated Ca²⁺release channels are widely expressed in virtually all tissues in murine embryos. As organogenesis proceeds, more specialized RyR channels are expressed in many cell types and the triggering mechanisms for intracellular Ca²⁺release become more diverse to include IP3-dependent and voltage-dependent and Ca²⁺-induced Ca²⁺release. As development proceeds virtually all cell types continue to express IP3R channels but in excitable cells including skeletal and cardiac muscles the major Ca²⁺release channels are RyRs. This developmental switch from predominantly IP3-mediated to both IP3-mediated and IP3-independent pathways for intracellular Ca²⁺release is consistent with data showing that IP3R plays an important regulatory role in cellular proliferation and apoptosis, whereas RyR is required for other cellular functions including muscle contraction.