11β-Hydroxysteroid dehydrogenase catalyses the conversion of cortisol to inactive cortisone. In kidney, the enzyme confers aldosterone-specificity on mineralocorticoid receptors by preventing their occupancy by cortisol. The expression of 11β-dehydrogenase in many extra-renal sites suggests that it has a wide role in modulating cortisol sensitivity. When renal 11β-dehydrogenase is defective (as occurs in congenital deficiency and after inhibition of the enzyme by liquorice or carbenoxolone) cortisol-dependent mineralocorticoid excess and hypertension ensue. In this thesis I address the hypotheses that: (i) in addition to its role in the kidney, 11β-dehydrogenase modulates the cortisol sensitivity in vascular smooth muscle; (ii) 11β-dehydrogenase is regulated physiologically by the hypothalamic-pituitary-adrenal axis; and (iii) deficiency of 11β-dehydrogenase, associated with increased cortisol sensitivity either in kidney or in blood vessels, contributes to pathophysiology in other forms of hypertension, specifically ectopic ACTH syndrome and essential hypertension. I show that 11β-dehydrogenase immunoreactivity and mRNA are localised to vascular smooth muscle cells in the rat, and bioactivity is greater in resistance vessels than conduit arteries. In support of a diverse role for the enzyme in modulating vascular tone I demonstrate: (i) potentiation of vasoconstrictor sensitivity of cortisol - and thereby to noradrenaline - in the forearm and dermis of men given enzyme inhibitors or congenitally deficient in 11β-dehydrogenase; and (ii) attentuation of noradrenaline reactivity by glucocorticoids in rat aorta which is increased following in vitro carbenoxolone administration. By studying in vitro affinities of rat vascular 11β-dehydrogenase for its cofactors I demonstrate its similarity to the hepatic isoform of the enzyme, and distinguish it from that in kidney. Moreover, vascular but not renal 11β-dehydrogeanse is induced by in vivo administration of glucorticoids. By contrast, ACTH is without effect on 11β-dehydrogenase activity in adrenalectomised rats, but inhibits the peripheral conversion of cortisol to cortisone in man. By selective venous catheterisation studies I confirm that the major site for this conversion is the kidney. Thus ACTH, in addition to stimulating cortisol synthesis, may stimulate the secretion of an 11β-dehydrogenase inhibitor from the adrenal, and thereby increase renal sensitivity to cortisol.