We tested the feasibility of real-time, 3-D ultrasound (US) imaging in the brain. The 3-D scanner uses a matrix phased-array transducer of 512 transmit channels and 256 receive channels operating at 2.5 MHz with a 15-mm diameter footprint. The real-time system scans a 65 degrees pyramid, producing up to 30 volumetric scans per second, and features up to five image planes as well as 3-D rendering, 3-D pulsed-wave and color Doppler. In a human subject, the real-time 3-D scans produced simultaneous transcranial horizontal (axial), coronal and sagittal image planes and real-time volume-rendered images of the gross anatomy of the brain. In a transcranial sheep model, we obtained real-time 3-D color flow Doppler scans and perfusion images using bolus injection of contrast agents into the internal carotid artery.