The application of short pulses of focused ultrasound was studied as a method of modifying electrically evoked responses in the mammalian brain. The in vitro hippocampal preparation was employed to facilitate delivery and dosimetry of ultrasound, and assessment of mechanisms of ultrasound effects. Cellular and dendritic field potential responses evoked by electrical stimulation of the Schaffer/Commissural afferents were examined before, during and after exposure of a portion of the CA1 region to focused ultrasound pulses for periods ranging from 2 to 15 min. Focused ultrasound with a repetition rate of 150 kHz was delivered in pulses comparable in duration to an electrical pulse that could initiate activity in the nervous system. The pulses had a center frequency of 750 kHz, durations of about 6 microseconds, and spatial-peak-temporal-averaged intensities of about 80 W/cm2. These parameters are markedly different from those employed in conventional diagnostic ultrasound. Temperatures in the bath and tissue were monitored. Extracellular field potentials reflecting the presynaptic fiber volley, dendritic response and cellular discharge were significantly reduced by exposure to ultrasound. Recovery occurred to varying degrees, and in one experiment was complete. Average temperature changes observed were less than 1 degree C. The present study demonstrates that the electrically evoked response in mammalian brain can be altered by ultrasound in a non-thermal, non-cavitational mode, and that such effects are potentially reversible.