ACTH and adrenocortical steroids have been known to raise blood pressure since their introduction into clinical practice. Our experimental studies in normal subjects show that ACTH reproducibly increases blood pressure in association with a rise in cardiac output, plasma and extracellular fluid volumes and exchangeable sodium. The rise in pressure is adrenally dependent and appears due to ACTH-induced increases in cortisol secretion. When ACTH is given by constant intravenous infusion, rates as low as 50 micrograms/day raise pressure. The increase in blood pressure is not dependent on, but modified by, dietary sodium content. Synthetic steroids (prednisolone, methylprednisolone, triamcinolone, dexamethasone) raise pressure in the absence of any increase in plasma volume or urinary sodium retention. Cortisol increases pressor responsiveness to endogenous and exogenous catecholamines, without evidence of any increase in sympathetic nervous activity. The role of this increased pressor responsiveness in ACTH/steroid-induced hypertension remains to be determined. There is some evidence from human studies that steroids may raise pressure by a hypertensinogenic mechanism, distinct from classical mineralocorticoid or glucocorticoid effects.