The hypothesis that abnormalities of calcium homeostasis at both an organ and cellular level are a primary factor in the pathogenesis of human and experimental hypertension forms the basis of this review. The rapidly expanding data base relating disordered calcium metabolism to altered vascular smooth muscle function and increased peripheral vascular resistance is summarized and integrated with the observations that reduced dietary calcium intake is the most consistent nutritional correlate of hypertension in the United States. The role of sodium and sodium chloride in pathogenesis of hypertension is reassessed in the light of new data from epidemiological clinical research, experimental models, and cell physiology investigations. The data supporting the thesis that the effects of sodium or chloride or both on blood pressure may represent, in selected situations, secondary influences mediated through induced changes in calcium homeostasis are presented. The interface between these nutritional factors and the normal regulation of vascular smooth muscle is discussed, providing a theoretical framework in which to assess the current information and to formulate the necessary future research.