Regional cerebral blood flow (rCBF) was examined following single episodes of cortical spreading depression (CSD) in rat brain after an intravenous bolus injection of [14C]iodoantipyrine. Cortical rCBF decreased to approximately 75% of control values during the first 60 min after CSD. This change was succeeded at 90-105 min by a small, transient flow increase. rCBF returned to normal at 120 min after CSD, and remained normal for the following 2 h. The same sequence of rCBF changes has been recorded in patients during migraine attacks. This study therefore supports the notion that CSD may serve as an animal model of migraine.