Abstract High-frequency deep brain stimulation (DBS) of sensorimotor thalamus containing ‘tremor cells’ leads to tremor arrest in humans with parkinsonian and essential tremor. To examine the possible underlying mechanism(s), we recorded in vitro intracellular responses of rat thalamic neurons to local intrathalamic stimulation. Such simulated DBS (sDBS) induced a sustained membrane depolarization accompanied by an increase in apparent membrane conductance in both motor and sensory neurons. With stimulation frequency above approximately 100 Hz, the sDBS-induced depolarization most typically led to repetitive neuronal firing or less frequently resulted in a complete blockade of action potential genesis. When regular intracellular current pulses were injected into cells to mimic ‘tremor’ activity, such rhythmic discharges were invariably disrupted or abolished by the random spike firing induced during high-frequency sDBS. Low-frequency sDBS left rhythmicity unaffected. We conclude that clinical thalamic DBS may lead to a neuronal de-rhythmicity and tremor stoppage through masking and/or blocking rhythmic firing of tremor cells.