Acute stress is associated with increased cardiovascular risk (1). The autonomic nervous system and hypothalamic-pituitary-adrenal axis are activated during stressful events and result in an acute surge in cortisol. In rats, glucocorticoid administration acutely reduces cardiovagal baroreflex sensitivity (2). It is not presently known whether this occurs in humans, but this is important to ascertain as it may contribute to the acute stress-induced increase in cardiovascular risk. To determine the effects of hydrocortisone on cardiovagal baroreflex sensitivity in healthy humans, 10 healthy males (mean±SD 29±5 yrs, 23±3 kg/m2) received a single intravenous bolus of hydrocortisone (200 mg) and placebo (saline) one week apart according to a randomized single-blinded cross over design. Three hours after hydrocortisone administration heart rate (HR) and blood pressure (BP) were recorded at rest and during sequential sodium nitroprusside and phenylephrine infusion (modified Oxford technique, MOT). Cardiovagal baroreflex sensitivity was determined from the slope of the systolic BP versus R-R interval during the phenylephrine induced rise in BP. Heart rate variability was assessed using the square root of the mean of the sum of the squares of differences between successive R-R intervals (rMSSD) to provide an index of cardiac parasympathetic activity. Statistical differences were determined using a one way ANOVA (serum cortisol) and paired t test (HR, BP, cardiovagal baroreflex sensitivity, rMSSD). Non-parametric data was transformed. A P value of less than 0.05 was considered statistically significant. Serum cortisol increased 3 hours after hydrocortisone administration (mean difference±SD +1649±623 nmol/L, p<0.05; hydrocortisone vs. placebo). Compared to placebo, resting HR (+7±4 beats/min; p<0.001) and systolic BP (+5±5 mmHg; p<0.05) were increased, whilst cardiovagal baroreflex sensitivity (-10±2 ms/mmHg, p<0.05) and rMSSD were decreased (-25±21 ms, p<0.05) 3 hours following hydrocortisone infusion. Our data show that cortisol administration acutely reduces cardiovagal baroreflex sensitivity and cardiac parasympathetic activity, possibly via a central mechanism. These findings suggest that the acute surge in cortisol accompanying stress may result in adjustments of cardiac autonomic control that could contribute to an increased cardiovascular risk.