Ghrelin is a newly discovered peptide, which is released from the stomach and neurons in the hypothalamic arcuate nucleus (ARC), and potently stimulates growth hormone release and food intake. In the present study, we investigated the effect of ghrelin on [Ca2⁢]i in thyroid FRTL-5 cells. Ghrelin (5 nM) increased [Ca2⁢]i and TSH (1 unit/l) had an additive effect on [Ca2⁢]i when extracellular normal solution was 1.1mM Ca2⁢ containing Coon's modified Ham's F12 medium. When Ca2⁢-free medium containing 2 mM EGTA replaced the above normal solution, ghrelin also induced a similar rise in [Ca2⁢]i. In the middle of [Ca2⁢]i increment by ghrelin, nifedipine (1μM), nickel (100μM) and La3⁢ (100μM) had no effect on [Ca2⁢]i. After endoplasmic reticulum was depleted by cyclopiazonic acid (CPA;10μM), ghrelin caused no visible change on [Ca2⁢]i in Ca2⁢-free/2 mM EGTA solution. These results suggest that ghrelin can increase [Ca2⁢]i through endoplasmic reticulum in thyroid FRTL-5 cells.