In the last two decades, major progress has been made in understanding the role of calcium (Ca) metabolism in blood pressure (BP) control. This article discusses the intracellular Ca handling systems that could potentially be involved in the pathogenesis of primary hypertension. We begin by reviewing our current knowledge of intracellular Ca handling, alterations of intracellular Ca metabolism in primary hypertension, and possible mechanisms of BP control. We have analyzed data on the structure and alternative splicing of major genes controlling intracellular free Ca concentration, ie, genes encoding intracellular Ca-binding protein (calmodulin, calbindin, plasma membrane Ca2+ pump, Na+/Ca2+ exchanger, and voltage-dependent Ca channels). Data are presented on the relationship of gene polymorphism and alternative splicing with membrane architecture and the function of gene products. Numerous observations on abnormalities of these gene products in primary hypertension are summarized. Studies on the polymorphism of genes regulating intracellular Ca in hypertension are only now being performed.