Patients with primary hyperparathyroidism (HPT) often have raised blood pressure but a simple cause-and-effect relationship has not been established. In 33 persons with probable primary HPT and mild hypercalcemia detected in a health survey, diastolic blood pressure (DBP) was significantly higher than among age- and sex-matched, normocalcemic, controls (89.4 +/- 9.8 (SD) v 85.2 +/- 8.9 mm Hg; P less than 0.05). Among the hypercalcemic individuals, DBP was, in a multivariate analysis, inversely related to the serum calcium and plasma-ionized calcium concentrations and to the serum levels of parathyroid hormone. A prospective, placebo-controlled, double-blind, study evaluating the effects of active vitamin D, alphacalcidol, (1 microgram daily) was carried out in the hypercalcemic patients over a six-month period. This treatment caused a slight further increase (0.05 mmol/L) of both serum calcium and plasma-ionized calcium concentrations. At the same time there was a significant reduction of DBP with a mean of 6.7 mm Hg compared with placebo (P less than 0.05). The hypotensive action of the vitamin D compound was inversely related to the pretreatment serum levels of 1,25(OH)2D3 and additive to concomitant, unchanged, antihypertensive medications. The negative correlation between serum calcium and blood pressure is similar to that obtained in normocalcemic individuals and suggests that raised blood pressure, at least in the milder forms of primary HPT, is only independently associated with the disease. Active vitamin D, although it raises serum calcium, can lower blood pressure also in hypercalcemic patients as previously demonstrated in normocalcemic individuals.