The purpose of this study was to test the hypothesis that plasma galanin concentration (pGal) is regularly increased in healthy humans with extensive orthostatic stress. Twenty six test persons (14 m, 12 f) were brought to an orthostatic end point via a progressive cardiovascular stress (PCS) protocol consisting of 70 degrees head-up tilt plus increasing levels of lower body negative pressure (LBNP) until either hemodynamically defined presyncope (PRES) or other signs of orthostatic intolerance (INT) occurred (nausea, clammy skin, excessive sweating, pallor of the skin). We further tested for possible gender, gravitational, and muscular training influences on plasma pGal responses: PCS was applied before and after three weeks of daily G_Z exposure training on a Human Powered Centrifuge (HPC). Test persons were randomly assigned to active (with bicycle work) or passive (without work) groups (seven men, six women in each group). Resting pGal was 26±3 pg/ml in men and 39±15 pg/ml in women (n.s.); women had higher galanin responses (4.9 fold increase) than men (3.5 fold, p=0.017) to PCS exposure. Overall, PCS increased pGal to 186±5 pg/ml (p=0.0003), without significant differences between PRES vs. INT, pre- vs. post-HPC, or active vs. passive gravitational training. Increases in pGal were poorly related to synchronous elevations in plasma vasopressin. We conclude that galanin is regularly increased in healthy humans under conditions of presyncopal orthostatic stress, the response being independent of gravity training but larger in females than in males.