1. In humans, the hypertensive effects of adrenocorticotropic hormone (ACTH) infusion are reproduced by intravenous or oral cortisol. Oral cortisol increases blood pressure in a dose-dependent fashion. At a dose of 80-200 mg/day, the peak increases in systolic pressure are of the order of 15 mmHg. Increases in blood pressure are apparent within 24 h. 2. Cortisol-induced hypertension is accompanied by a significant sodium retention and volume expansion. Co-administration of the type I (mineralocorticoid) receptor antagonist spironolactone does not prevent the onset of cortisol-induced hypertension. Thus, sodium retention is not the primary mechanism of cortisol-induced hypertension. 3. Direct and indirect measures of sympathetic activity are unchanged or suppressed during cortisol administration, suggesting that cortisol-induced hypertension is not mediated by increased sympathetic tone. 4. Preliminary evidence in humans suggests that suppression of the nitric oxide system may play a role in cortisol-induced hypertension. 5. These potential mechanisms of cortisol action may be relevant in a number of clinical contexts, including Cushing's syndrome, apparent mineralocorticoid excess, the hypertension of liquorice abuse and chronic renal failure. There is also preliminary evidence suggesting a role for cortisol in essential hypertension.