To examine the effects of hypertonic/hyperoncotic treatment on physiologic variables and regional cerebral blood flow and to test its neuroprotective efficiency in a model of permanent venous ischemia. Randomized prospective study. University research institute. Adult male Wistar rats, weighing 359 +/- 54 g (n = 38). Rats were subjected to photochemical occlusion of two adjacent cortical veins. A randomized infusion with vehicle (0.9% NaCl), 10% hydroxyethyl starch 200,000 (HES), or 7.5% saline plus 10% hydroxyethyl starch 200,000 (HHES) was started 30 mins after two-vein occlusion. Effects on physiologic variables and regional cerebral blood flow (assessed by laser Doppler flowmetry) were studied up to 120 mins after two-vein occlusion. Two days after occlusion, the brains were removed for histologic evaluation. After occlusion, regional cerebral blood flow decreased by 50%, significantly in all groups (from 47.3 +/- 3 to 22.2 +/- 2.2 laser Doppler units). In the vehicle and HES groups, regional cerebral blood flow further decreased to 12.9 +/- 1.9 and 17.8 +/- 2.3 laser Doppler units, respectively. HHES improved regional cerebral blood flow significantly to 27.3 +/- 3.5 laser Doppler units, particularly by reducing no-flow/low-flow areas and reducing infarct size. We found that HHES reduced infarct size as a consequence of an improved regional cerebral blood flow and reduced no-flow/low-flow areas in the tissue at risk in the two-vein occlusion model.