Background: Thalamic deep brain stimulation ameliorates essential and parkinsonian tremors refractory to medications. Stimulus voltage, polarity configuration, frequency, and pulsewidth can each be adjusted in order to optimize tremor control and maximize battery life. The relative impacts of these programmable variables have not previously been quantified. Methods: The thalamus of 11 patients (bilaterally in 2) was studied 4 to 59 months postoperatively. The stimulator was inactivated and medications withheld for 12 hours, and optimal electrode contacts were selected. Stimulation followed at a range of voltages (0, 1, 2, 3, or 4 V), pulsewidths (60, 90, or 120 mus), and frequencies (130, 160, or 185 Hz) for both monopolar and bipolar configurations. Seventy-eight combinations of variables were programmed in random sequence. Postural and action tremors were measured with an electromagnetic tracker, tremor was subjectively graded, and side effects were noted. Results: Voltage was consistently predictive of tremor response. Mean postural tremor amplitude in PD fell from 6.4 em at 0 V to 2.6, 1.0, 0.3, and 0 cm at 1 through 4 V (bipolar configuration). The voltage response curve for essential tremor was flatter. The monopolar configuration was 10 to 25% more effective than bipolar. The longest pulsewidth tested was up to 30% more effective than the shortest, but frequency changes had little effect on tremor amplitude. Side effects occurred only with monopolar stimulation, and the only setting that was intolerable for the majority was 4 V, 120 mus, and 185 Hz. Conclusion: Bipolar deep brain stimulation at 90 mus, 130 Hz, adjusting the voltage up to 3 V, tends to be effective and well tolerated. Monopolar provides similar benefits for lower voltage, but side effects become common at 3 or 4 V.