Patients with cirrhosis have a hyperdynamic circulation and an abnormal blood volume distribution with central hypovolemia, an activated sympathetic nervous system (SNS) as well as the renin-angiotensin-aldosterone system (RAAS). As the hyperdynamic circulation in cirrhosis may be present only in the supine patient, we studied the humoral and central hemodynamic responses to changes with posture. Twenty-three patients with alcoholic cirrhosis (Child-Turcotte-Pugh classes A/B/C: 2/13/8) and 14 healthy controls were entered. Measurements of central hemodynamics and activation of SNS and RAAS were taken in the supine position, after 30° head-down tilting, and after 60° passive head-up tilting for a maximum of 20 minutes. After the head-up tilting, the central blood volume (CBV) decreased in both groups, but the decrease was significantly smaller in patients than in controls (−19% vs. −36%, P < .01). Central circulation time increased only in the patients (+30% vs. −1%, P < .01). The absolute increases in circulating norepinephrine and renin after head-up tilting were significantly higher in the patients than in the controls (P < .05 and P < .01, respectively). In patients with cirrhosis, changes in SNS and RAAS were related to changes in arterial blood pressure, systemic vascular resistance, heart rate, non-CBV, plasma volume, and arterial compliance. In conclusion, cardiovascular and humoral responses to changes in posture are clearly abnormal in patients with cirrhosis. Head-up tilting decreases the CBV less in patients with cirrhosis, and the results suggest a differential regulation of central hemodynamics in patients with cirrhosis. (Hepatology 2004;40:811–819).