Large conduit arteries and cerebral autoregulation. There is a convincing body of evidence demonstrating that the large arteries of the brain play a much larger and more important role in the regulation of CBF than generally ascribed to them (Mchedlishvili, 1964; Mchedlishvili et al. 1973; Faraci & Heistad, 1990). Indeed, using a canine in situ ICA where the inlet pressure could be controlled, ICA constriction maintained pressure at the circle of Willis nearly constant in the face of increasing perfusion pressure (Mchedlishvili et al. 1973); the feline VA, in contrast, does not buffer increases in MAP (Faraci et al. 1987a). Another group, using a different in vivo technique that allowed calculation of the lumped resistance for all the large arteries in dogs and cats (Heistad et al. 1978a; Faraci et al. 1987a), found similar results, concluding that the large arteries were responsible for a quarter to half of the total cerebrovascular resistance during resting conditions.Perhaps because these larger arteries of the neck are generally considered to be ‘conduit’ arteries, the idea that they can actively participate in CBF regulation has not been embraced. However, in rabbits and dogs the inter- nal geometry of the ICA and VA was found to change considerably where the vessels bend, at the cavernous sinus for the ICA (the carotid siphon) and at the V3 segment of the VA at the entrance of the foramen magnum (Mchedlishvili, 1964). The turbulent flow resulting from such luminal diameter changes within tortuous segments must dramatically increase resistance compared with non-tortuous segments. That is to say that a smaller decrease in lumen diameter would be required to produce a given increase in resistance within the carotid siphon and V3 segment of the VA (Fig. 1, inlay I).Recent human MRI data showing complex non-Newtonian flow and attenuated pulsatility along the carotid siphon support this theory (Takeuchi & Karino, 2010; Schubert et al. 2011). In humans, these vessels change diameter in response to changes in PaCO2 and PaO2 (Wilson et al. 2011; Willie et al. 2012); future studies using such advanced imaging techniques should assess whether they are also involved in the cerebrovascular response to acute changes in MAP.