Inositol 1,4,5-trisphosphate (IP3) stimulates Ca$\mathrm{<mrow\; data-mjx-texclass="ORD">2+</mrow>}$ release from the endoplasmic reticulum (ER), and the response is potentiated by 3',5'-cyclic AMP (cAMP). We investigated this interaction in HEK293 cells using carbachol and parathyroid hormone (PTH) to stimulate formation of IP$\mathrm{<mrow\; data-mjx-texclass="ORD">3</mrow>}$ and cAMP, respectively. PTH alone had no effect on the cytosolic Ca$\mathrm{<mrow\; data-mjx-texclass="ORD">2+</mrow>}$ concentration, but it potentiated the Ca$\mathrm{<mrow\; data-mjx-texclass="ORD">2+</mrow>}$ signals evoked by carbachol. Surprisingly, however, the intracellular Ca$\mathrm{<mrow\; data-mjx-texclass="ORD">2+</mrow>}$ stores that respond to carbachol alone could be both emptied and refilled without affecting the subsequent response to PTH. We provide evidence that PTH unmasks high-affinity IP$\mathrm{<mrow\; data-mjx-texclass="ORD">3</mrow>}$ receptors within a discrete Ca$\mathrm{<mrow\; data-mjx-texclass="ORD">2+</mrow>}$ store. We conclude that Ca$\mathrm{<mrow\; data-mjx-texclass="ORD">2+</mrow>}$ stores within the ER that dynamically exchange Ca$\mathrm{<mrow\; data-mjx-texclass="ORD">2+</mrow>}$ with the cytosol maintain a functional independence that allows one store to be released by carbachol and another to be released by carbachol with PTH. Compartmentalization of ER Ca$\mathrm{<mrow\; data-mjx-texclass="ORD">2+</mrow>}$ stores adds versatility to IP$\mathrm{<mrow\; data-mjx-texclass="ORD">3</mrow>}$-evoked Ca$\mathrm{<mrow\; data-mjx-texclass="ORD">2+</mrow>}$signals.