We hypothesized that the response of cerebral blood flow (CBF) to changing viscosity would be dependent on "baseline" CBF, with a greater influence of viscosity during high-flow conditions. Plasma viscosity was adjusted to 1.0 or 3.0 cP in rats by exchange transfusion with red blood cells diluted in lactated Ringer solution or with dextran. Cortical CBF was measured by H₂ clearance. Two groups of animals remained normoxic and normocarbic and served as controls. Other groups were made anemic, hypercapnic, or hypoxic to increase CBF. Under baseline conditions before intervention, CBF did not differ between groups and averaged 49.4 ± 10.2 ml · 100 g¹ · min¹ (±SD). In control animals, changing plasma viscosity to 1.0 or 3.0 cP resulted in CBF of 55.9 ± 8.6 and 42.5 ± 12.7 ml · 100 g¹ · min¹, respectively (not significant). During hemodilution, hypercapnia, and hypoxia with a plasma viscosity of 1.0 cP, CBF varied from 98 to 115 ml · 100 g¹ · min¹. When plasma viscosity was 3.0 cP during hemodilution, hypercapnia, and hypoxia, CBF ranged from 56 to 58 ml · 100 g¹ · min¹ and was significantly reduced in each case (P < 0.05). These results support the hypothesis that viscosity has a greater role in regulation of CBF when CBF is increased. In addition, because CBF more closely followed changes in plasma viscosity (rather than whole blood viscosity), we believe that plasma viscosity may be the more important factor in controlling CBF.