To examine the relative importance of 1) reduced blood viscosity, 2) vasodilation mediated through beta-adrenergic receptors, and 3) sympathetic nerve activity on the regulation of limb blood flow during anemia, norepinephrine (NE) was infused in 10 anesthetized-paralyzed dogs at normal and reduced hematocrit (Hct). Cardiac output (QT), limb and total oxygen uptake (VO2)n and limb venous flow (QL) were determined. After a control period, NE (2 micrograms . kg-1 . min-1) was infused followed by another control period. The Hct was then reduced to 9% by isovolemic hemodilution with dextran, and data were obtained during anemia, anemia plus NE, and after isovolemic reinfusion of red blood cells (Hct 25%) during NE. Another 10 dogs were treated identically after propranolol (1.0 mg/kg) administration. At normal Hct, NE increased limb resistance (RL) (P less than 0.01) in the beta-block group; a decrease in RL (P less than 0.05) and a rise in QL (P less than 0.01) occurred in the no block group. QL and VO2 (limb and total) were not changed by NE. During anemia, RL was not altered in either group by NE; QT fell (P less than 0.05) in both, and QL decreased in the no block group. After reinfusion of cells, NE produced an increase in RL and total peripheral resistance (P less than 0.01) and a fall in QL (P less than 0.01) and QT (P less than 0.01) in both groups; limb and total VO2 rose in the no block group. We conclude that the reduction in viscosity prevented an increase in both RL and redistribution of QL during severe anemia (Hct 9%).