Cardiovascular modifications, specially orthostatic intolerance (OI) are well known after spaceflight or long duration head-down bed-rest (HDBR) There is no agreement about their mechanisms. The aim of the study was to compare OI after a 42 day HDBR (n = 7) and after a 90 to 198 day spaceflight (n = 10). The studies were made during a stand test of 10 minutes for HDBR following 10 min in supine position and 5 min in sitting position. In both groups the variables measured were blood pressure (BP by transcutaneous plethysmography, Finapres) and ECG for RR interval (RRi) determination which allowed us to calculate autonomic indexes by spectral analysis of RRi and to determine spontaneous baroreflex sensitivity. In the cosmonaut group, 1 subject experienced a vaso-vagal syncope and 2 asked to stop the test without a decrease in BP. In HDBR, 4 subjects out of 7 did not perform the whole stand test (1 vaso-vagal syncope, 1 tachycardia and 2 hypotensions). Cosmonauts or HDBR subjects had common profiles: tachycardia and a decrease in parasympathetic index and baroreflex sensitivity. Both groups have an OI (30% of the subjects). However the mechanisms are different even if they have a common postural orthostatic tachycardia syndrome (POTS). The spaceflight duration was not determinant and we have no indice to predict OI which was one of the aims of the study.