The aim of this study was to determine the effects of a 5-h weightlessness simulation (using supine bed rest or head-down tilt at -10 degrees = HDT) on plasma renin activity (PRA), aldosterone (PA), and catecholamines (epinephrine-E, norepinephrine-NE, and dopamine-DA) and to compare the results with those obtained with horizontal bed rest (BR), which is often taken as a control situation for simulation studies. Ten healthy young volunteers submitted to the three following postural tests: 7 h sitting; 1 h sitting, 5 h supine, and 1 h sitting; 1 h sitting, 5 h HDT, and 1 h sitting. Our results show that a 5-h HDT or BR induced a significant progressive increase in plasma volume (14.5% for HDT and 7% for BR) and a decrease in diastolic blood pressure (18% for HDT and 17% for BR), PRA (60% for HDT and 40% for BR), PA (63% for HDT and 60% for BR), and NE (20% for HDT and 25% for BR) compared to the sitting position. E decreased only in HDT, and DA was unchanged. We concluded that the main part of the cephalad shift is achieved by bed rest as reflected by changes in hematocrit and plasma protein concentration. The decrease in diastolic blood pressure, the inhibition of the renin-angiotensin aldosterone system (in part explained by a decrease in NE) are similar in BR and HDT. We demonstrate that the use of a relevant body position as control is a major concern when investigating the hormonal effects of HDT. If recumbency is chosen as the control situation in HDT studies, it is not surprising to observe only few changes when HDT is applied.