 Tetrahydrobiopterin BH4 is a cofactor for the nitric oxide NO synthase enzymes, such that its insufficiency results in uncoupling of the enzyme, leading to release of superoxide rather than NO in disease states, including hypertension. We hypothesized that oral BH4 will reduce arterial blood pressure BP and improve endothelial function in hypertensive subjects. Oral BH4 was given to subjects with poorly controlled hypertension BP 13585 mm Hg and weekly measurements of BP and endothelial function made. In Study 1, 5 or 10 mg kg1 day1 of BH4 n8 was administered orally for 8 weeks, and in Study 2, 200 and 400 mg of BH4 n16 was given in divided doses for 4 weeks 