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Hemodilution in the acute phase of ischemic stroke is still controversial. Multicenter studies have failed to demonstrate any benefit. The present study focuses attention on analysis of circulation in stroke and on individual restabilization of circulation.The Amsterdam Stroke Study is a prospective, single-center, randomized clinical trial (n=300). Normovolemic hemodilution is accomplished in a customized procedure by administration of 20% albumin plus crystalloids under hemodynamic and rheological monitoring in the acute phase of stroke. All patients receive general intensive care treatment and monitoring with a pulmonary artery catheter. This custom-tailored fluid therapy is guided on the basis of a target pulmonary capillary wedge pressure (12±3 mm Hg) and hematocrit (0.32±0.02). The control group receives only customized rehydration by infusion of crystalloids.We obtained significant (p<0.05) reduction in mortality at 3 months (from 27% to 16%) and an increase in independence at home (from 35% to 48%) after viscosity reduction by means of hemodilution with albumin in the subgroup with a hematocrit <0.45 (n=201) (specific viscosity effect). We also obtained a significant (p<0.005) reduction in mortality at 3 months (from 27% to 8%) and an increase in independence (from 35% to 59%) after only rehydration with crystalloids in the subgroup with overt dehydration (hematocrit ≥0.45; n=51) as compared with the normal-hematocrit group without signs of dehydration (hematocrit <0.45; n=103) (specific rehydration effect).This study may provide an explanation for the failures in former hemodilution trials and may re-establish proper hemodilution and rehydration as a valuable therapy in the acute phase of stroke, thus reducing mortality and improving independence after 3 months.