Oral hydrocortisone increases blood pressure and enhances pressor responsiveness in normal human subjects. We studied the effects of 1 week of oral hydrocortisone (200 mg/day) on blood pressure, cardiac output, total peripheral resistance, forearm vascular resistance, and norepinephrine spillover to plasma in eight healthy male volunteers. Although diastolic blood pressure remained unchanged, systolic blood pressure increased from 119 to 135 mm Hg (SED +/- 3.4, p less than 0.01), associated with an increased cardiac output (5.85-7.73 l/min, SED +/- 0.46, p less than 0.01). Total peripheral vascular resistance fell from 15.1 to 12.2 mm Hg/l/min (SED +/- 1.03, p less than 0.05). Resting forearm vascular resistance remained unchanged, but the reflex response to the cold pressor test was accentuated, the rise in resistance increasing from 10.5 mm Hg/ml/100 ml/min (R units) before treatment to 32.6 R units after treatment (SED +/- 6.4, p less than 0.025). The rise in forearm vascular resistance accompanying intra-arterial norepinephrine (25, 50, and 100 ng/min) was also significantly greater after hydrocortisone, increasing from an average of 14.9 +/- 2.4 R units before treatment to 35.1 +/- 5.5 R units after hydrocortisone (SED +/- 6.0, p less than 0.05). A shift to the left in the dose-response relation and fall in threshold suggested increased sensitivity to norepinephrine after treatment. Measurement of resting norepinephrine spillover rate to plasma and norepinephrine uptake indicated that overall resting sympathetic nervous system activity was not increased. The rise in resting blood pressure with hydrocortisone is associated with an increased cardiac output (presumably due to increased blood volume).(ABSTRACT TRUNCATED AT 250 WORDS)