Summary The effects of open-heart surgery and total body perfusion on blood viscosity and related factors were studied in 31 patients. The oxygenator was primed with whole blood in 17 cases and with diluted blood in 14. In all patients, but to a greater degree in the hemodiluted group, blood viscosity fell to levels lower than would be expected on the basis of hematocrit. This decrease was accompanied by a fall in plasma viscosity, which, in turn, coincided with an increase in plasma water content and a decrease in plasma protein concentration. No change in the shear-rate dependence of blood viscosity was noted. Aqueous dilution is the prime determinant of blood viscosity during extracorporeal perfusion, regardless of the type of prime.