The association between excess glucocorticoids and hypertension has been much discussed but poorly understood. From both clinical observations and laboratory studies, it is clear that glucocorticoids exert their effects at many different sites responsible for blood pressure regulation. Isoforms of the enzyme 11ss-hydroxysteroid dehydrogenase (11ss-HSD), located in steroid-responsive tissues, metabolize endogenously produced glucocorticoids. These enzymes limit steroid access to mineralocorticoid and/or glucocorticoid receptors. In the kidney, synthetic and endogenous glucocorticoids are capable of enhancing transepithelial sodium transport in the presence of 11ss-HSD inhibition. Proximal tubule reabsorption of sodium can be indirectly augmented after chronic exposure to glucocorticoids. In this segment, steroids have a permissive effect, increasing the expression of both Na(+), K(+) adenosine triphosphatase along the basolateral membrane and Na(+)-H(+) exchanger along the apical membrane of epithelial cells. Although glucocorticoids themselves produce no increase in sodium reabsorption in this segment, angiotensin II-stimulated sodium transport is significantly greater in proximal tubular cells pretreated with glucocorticoids. The increased transport in distal renal segments is more direct and stems in part from glucocorticoid cross-over binding to mineralocorticoid receptors. In vascular tissue, synthetic and endogenous glucocorticoids, after inhibition of the dehydrogenase reaction, magnify the response to circulating vasoconstrictors. The effects of glucocorticoids in vascular tissue is indirect, upregulating the expression of receptors to many vasoconstrictors and downregulating the effects of potential vasodilators. Thus, glucocorticoids have the potential to alter both circulating volume and vascular resistance.