The transmissible agent of Creutzfeldt-Jakob disease, a dementing neurodegenerative disorder, is present in many tissues of the body, even though its pathologic consequences are confined to the brain. Experimental animal models of the disease have shown that blood (most probably the leukocyte component) can be infectious in both the clinical and preclinical incubation stages of the disease, and there are also a few reported isolations of the agent from whole blood, buffy coats, or serum from humans with Creutzfeldt-Jakob disease. Despite this potential for blood-borne iatrogenic infection, epidemiologic studies do not support the contention that the administration of blood, blood components, or blood derivatives transmits the disease; in particular, not one of nearly 2000 patients who have been studied during the past two decades has been shown to have acquired the disease from a blood donor who later died of Creutzfeldt-Jakob disease. This fact does not diminish our responsibility to preclude such an occurrence from happening in the future, and will require an unremitting effort to screen from the blood donor population all individuals with a higher than average risk of harboring the infectious agent; namely, donors with neurologic disease, a family history of neurologic disease, or a history of events that have been identified as leading to iatrogenic Creutzfeldt-Jakob disease, such as neurosurgical procedures involving dura mater homografts or treatment with native pituitary hormones.