Several studies have shown that increased dietary calcium decreases blood pressure (BP) in spontaneously hypertensive rats (SHR), but the underlying mechanisms are not fully understood. We compared the effects of a high calcium diet and different antihypertensive agents on BP and intracellular free Ca2+ concentration ([Ca2+]i) in lymphocytes of adult SHR. The calcium content of the normal chow was 1.1% and that of the high calcium chow was 2.5%. Antihypertensive drug treatments were performed by giving the animals trichlormethiazide (2 mg/kg/day), atenolol (25 mg/kg/day), and quinapril (10 mg/kg/day) in drinking water. Untreated SHR and normotensive Wistar-Kyoto (WKY) rats served as controls. After 14 weeks of study systolic BP (SBP) and [Ca2+]i in blood lymphocytes, measured with a fluorescent indicator quin-2, were higher in untreated SHR than in WKY rats. Trichlormethiazide, atenolol, quinapril, and the high calcium diet all decreased BP in SHR, but only quinapril and calcium-rich diet concurrently reduced [Ca2+]i. We conclude that the reduction in [Ca2+]i during high calcium intake does not result from decreased BP itself. If the changes in lymphocyte [Ca2+]i reflect Ca2+ metabolism in other tissues as well, especially in vascular smooth muscle, the normalization of [Ca2+]i may be involved in the BP-lowering mechanisms of oral calcium loading and angiotensin-converting enzyme (ACE) inhibition in genetic hypertension.