The relationships between cerebral blood flow (CBF), arterial oxygen content, whole blood viscosity and the transport of oxygen to the brain have been studied in 54 subjects with variations in arterial oxygen content resulting from alterations in haemoglobin concentration ranging from 5.7 to 19.1 g/dl. A highly significant relationship was found between CBF and arterial oxygen content, CBF altering to maintain the rate of transport of oxygen to the brain within certain limits. No significant effect of changes in blood viscosity was evident. In a multiple regression analysis arterial oxygen content emerged as the major determinant of CBF and after this effect had been taken into account there was no significant influence of blood viscosity, arterial pCO2, age or mean arterial blood pressure. The results imply that the alterations in CBF found in subjects with anaemia and polycythaemia are primarily physiological and not caused by the accompanying alterations in blood viscosity. It is proposed that the response of the cerebral circulation to arterial oxygen content is mediated by a local mechanism sensitive to alterations in local tissue oxygen tension.