Dysregulations of calcium (Ca) homeostasis may be involved in the pathophysiology of bipolar disorder. Enhanced Ca response to various agonists in peripheral blood cells is one of a few confirmed biological markers for bipolar disorder. Recently, a polymorphism of XBP1, a pivotal gene in the endoplasmic reticulum (ER) stress response, was shown to contribute to the genetic risk factor for bipolar disorder. Thus, in this study, we examined the relationship between the XBP1 gene polymorphism and the Ca signaling in the platelets of healthy controls. The present results suggest no significant difference in the basal Ca level or 5-HT-induced Ca mobilization among normal subjects with -116C/C, C/G, and G/G genotypes. Further investigations are necessary to examine the relationship in the different peripheral blood cells and/or in larger samples from patients with bipolar disorder.