We considered that a moderate reduction of the central blood volume (CBV) may activate the coagulation system. Lower body negative pressure (LBNP) is a non-invasive means of reducing CBV and, thereby, simulates haemorrhage. We tested the hypothesis that coagulation markers would increase following moderate hypovolemia by exposing 10 healthy male volunteers to 10 min of 30 mmHg LBNP. Thoracic electrical impedance increased during LBNP (by 2.6 +/- 0.7 Omega, mean +/- SD; P < 0.001), signifying a reduced CBV. Heart rate was unchanged during LBNP, while mean arterial pressure decreased (84 +/- 5 to 80 +/- 6 mmHg; P < 0.001) along with stroke volume (114 +/- 22 to 96 +/- 19 ml min(-1); P < 0.001) and cardiac output (6.4 +/- 2.0 to 5.5 +/- 1.7 l min(-1); P < 0.01). Plasma thrombin-antithrombin III complexes increased (TAT, 5 +/- 6 to 19 +/- 20 microg l(-1); P < 0.05), indicating that LBNP activated the thrombin generating part of the coagulation system, while plasma D-dimer was unchanged, signifying that the increased thrombin generation did not cause further intravascular clot formation. The plasma pancreatic polypeptide level decreased (13 +/- 11 to 6 +/- 8 pmol l(-1); P < 0.05), reflecting reduced vagal activity. In conclusion, thrombin generation was activated by a modest decrease in CBV by LBNP in healthy humans independent of the vagal activity.