Brain stimulation methods are indispensable to the study of brain function. They have also proven effective for treating some neurological disorders. Historically used for medical imaging, ultrasound (US) has recently been shown to be capable of noninvasively stimulating brain activity. Here we provide a general protocol for the stimulation of intact mouse brain circuits using transcranial US, and, using a traditional mouse model of epilepsy, we describe how to use transcranial US to disrupt electrographic seizure activity. The advantages of US for brain stimulation are that it does not necessitate surgery or genetic alteration, but it confers spatial resolutions superior to other noninvasive methods such as transcranial magnetic stimulation. With a basic working knowledge of electrophysiology, and after an initial setup, ultrasonic neuromodulation (UNMOD) can be implemented in less than 1 h. Using the general protocol that we describe, UNMOD can be readily adapted to support a broad range of studies on brain circuit function and dysfunction. © 2011 Nature America, Inc. All rights reserved.