Single pulses of focused ultrasound have been observed to significantly modify neuronal excitability in vitro for a period of 40-50 ms following pulse termination. This window of transient modification includes periods of both relative suppression and enhancement of excitability, the sequences of which generally follow distinct temporal patterns. The ultrasound pulses were focused, 2-7 MHz, nominally of 500 microseconds duration, and of peak intensities of 100-800 W/cm2. Specific absorbed energies were less than 100 mJ/gm, which strongly precludes bulk thermal mechanisms as a basis of this effect. Our current evidence suggests that the low-frequency radiation pressure transient accompanying the envelope of the acoustic pulse is the proximal effector in this phenomenon, acting by the gating of relatively slow stretch-sensitive channels in the neuronal membrane. These observations demonstrate the potential for high peak-power, low total-energy pulses of ultrasound to functionally modulate neuroelectric signals, a finding which could suggest new prosthetic, analgesic, or therapeutic clinical applications.