The feasibility of controlled blood-brain barrier (BBB) disruption in rats was demonstrated with a low-frequency clinical transcranial MRI-guided focused ultrasound device that operates at 230 kHz (ExAblate Neuro, InSightec) combined with microbubbles. Thirty-six targets were sonicated in one hemisphere in each experiment under closed-loop control based on real-time recordings of acoustic emissions. Disruption was confirmed in maps of R1 relaxation following Gadavist administration. After three weekly BBB disruptions covering an entire hemisphere, we always produced BBB disruption with only minor vascular side effects. We also delivered irinotecan chemotherapy across the BBB without apparent neurotoxicity.