The incidence of cerebral damage in patients undergoing open-heart surgery still remains unacceptably high. Confusion exists in relation to the principal cause. The relative roles of altered perfusion of the cerebral circulation and the occurrence of diffuse microembolism are subjects of a number of studies. The consensus is increasing that microembolism is the most important cause. This paper reviews the significance of cerebral perfusion and the functional disturbances associated with nonpulsatile cardiopulmonary bypass. It also considers in more detail the occurrence of microembolism, both gaseous and particulate. Rational therapy related to an understanding of the primary cause is considered, with particular respect to the use of small pore filtration, inhibitors of platelet aggregation (e.g. prostacyclin), and the possible use of cerebral protective drugs.