We used 44 splenectomized dogs to study the effects of isovolemic hemodilution with a crystalloid solution. The dogs were randomly divided into a hemodilution and a control group. In each group, 17 dogs were subjected to 6 hours of internal carotid and middle cerebral artery occlusion, and five dogs received sham operations. Isovolemic hemodilution by phlebotomy and Ringer's lactate infusion was performed 30 minutes after arterial occlusion and resulted in an average hematocrit of 32-33%. Hemodilution significantly reduced viscosity, fibrinogen and total protein concentrations, and plasma oncotic pressure. Systemic arterial blood pressure and pulmonary wedge pressure decreased slightly with hemodilution, but central venous pressure and pulmonary arterial pressure did not change significantly. There was a similar decrease in cardiac index in both hemodiluted and control dogs, which may have been due to the effects of barbiturate anesthesia. Intracranial pressure increased significantly with time in all dogs subjected to arterial occlusion, but this increase was significantly more severe in the hemodiluted dogs. Specific gravity, measured just after the dogs were killed, 6 hours after hemodilution, was significantly lower in the white matter and basal ganglia of the left (ischemic) hemisphere in hemodiluted dogs than in controls. Regional cerebral blood flow decreased significantly in the left hemisphere after arterial occlusion. This decrease was almost completely reversed by hemodilution except in the basal ganglia, where the increase in edema caused by hemodilution was the greatest.