Improvement of hemorheology is one of the most important approaches in the treatment of acute ischemic stroke. We investigated the influence of extracorporal rheopheresis (ER) on cerebral blood flow in patients with acute ischemic stroke and evaluated its therapeutic effect. Thirty-three patients (rheopheresis group, 17; control group, 16; mean age 64 +/- 10 years) with acute ischemic stroke were included in our prospective randomized trial. The first treatment was started within 12 h after onset of symptoms, and treatment was repeated 3 times at an interval of 24 h. Hemorheological parameters were measured before and after each session. The cerebral blood flow was analyzed using 99mTc-ECD-SPECT. The functional and neurological outcomes were determined by follow-up investigations after 3 months. The hemorheological parameters were significantly different between the rheopheresis group (18% decrease of plasma viscosity, 55% decrease of red blood cell aggregation) and the control group (no decrease of both parameters). The single photon emission computed tomography (SPECT) analysis showed early reperfusion in 35% of the patients treated with rheopheresis and in 37% of the control group (NS). There were no differences in the neurological outcomes between the 2 groups. Extracorporal rheopheresis is practicable and safe. It rapidly and consistently improved the hemorheological parameters. Although this did not impact on cerebral perfusion or clinical outcome in patients with acute ischemic stroke in this report, we propose that ER deserves to be further evaluated by initiating the first treatment within 6 h post-insult.