A role for calcium in human hypertensive disease has been suggested. However, the various, apparently contradictory, abnormalities of calcium metabolism observed in experimental and clinical hypertension do not allow for unambiguous description of the specific manner in which calcium contributes to the hypertensive process. We studied calcium metabolism in essential hypertension and used renin-sodium profiling, which reveals the biochemical heterogeneity of clinical hypertension. We observed renin-linked, heterogeneous deviations in circulating levels of the divalent cations, magnesium and ionized calcium, in addition to deviations in the calcium-regulating hormones, parathyroid hormone (PTH), calcitonin (CT), and 1,25 dihydroxyvitamin D (1,25 D). These renin-calcium metabolic deviations may both predict and contribute to the pathophysiology of salt-induced hypertension, the blood pressure effects of oral calcium supplementation, as well as the short and longer term effectiveness of calcium channel blockade. Altogether, these data suggest an intimate linkage between the hormonal control of calcium metabolism, the renin-angiotensin system and blood pressure regulation in human hypertension.