Although abnormalities of calcium metabolism have been described in various hypertensive states, the specific manner in which these abnormalities contribute to the increased pressure remains unclear. Our own group, in attempting to resolve the seemingly contradictory evidence thus far obtained, has adopted an approach emphasizing the clinical as well as biochemical heterogeneity among hypertensive subjects. We have observed the following: broad-based deviations of calcium ionic and hormonal indices in patients with essential hypertension; these deviations are linked with concurrent deviations in the renin-aldosterone system. Thus, low-renin subjects exhibit a calcium ionic and hormonal profile suggestive of calcium deficiency, whereas high-renin subjects have an opposite metabolic profile suggestive of calcium excess; blood pressure responses to dietary salt loading may also differ among renin subgroups of essential hypertension and may be mediated by salt-induced alterations of calcium metabolism. In the absence of these alterations, dietary salt intake results in little or no change in blood pressure; and calcium as a dietary supplement may itself possess antihypertensive properties in targeted subgroups of essential hypertensive patients, preferentially in low-renin, lower ionized calcium subjects. Interestingly, calcium channel blockade also preferentially lowers pressure in low-renin, lower serum ionized calcium forms of hypertension and may define those subjects whose elevated pressure is most dependent on extracellular calcium. Conversely, renin profiling or serum ionized calcium measurements may be used clinically to help target subjects most likely to benefit from calcium channel antagonists. Lastly, unlike other antihypertensive drug classes, high salt intake does not blunt, and may even enhance, the hypotensive effects of calcium channel blockade, lessening the need for stringent dietary recommendations. Altogether, these heterogeneous alterations of calcium metabolism in essential hypertension suggest that the linkage between the regulation of calcium metabolism, renin system activity, and blood pressure in essential hypertension is of pathophysiologic as well as therapeutic relevance.