Essential hypertension is a polygenic disorder with a complex and multifactorial nature. Although no single gene is responsible, multiple genes provide incremental contributions to this disorder. Vitamin D is a primary regulator of calcium homeostasis. Epidemiological and clinical studies appear to point to a role for vitamin D in hypertension but direct experimental evidence is lacking. Sprague-Dawley rats were made vitamin D deficient by feeding a purified vitamin D-deficient diet and eliminating all sources of ultraviolet light. Vitamin D deficiency was confirmed by very low serum calcium levels. Blood pressure was measured in conscious rats non-invasively with a volume pressure recording system. Vitamin D deficiency results in elevated blood pressures independent of serum calcium concentration. The administration of 1 alpha,25-dihydroxyvitamin D-3 (1,25-(OH)(2)D-3) and a less calcemic analog, 2-methylene-19-nor-20(S)-1 alpha hydroxyl-bishomopregnacalciferol (2MbisP) significantly reduced blood pressure in these rats. Thus, vitamin D status is one of the determining factors regulating blood pressure. (C) 2015 Elsevier Inc. All rights reserved.