Six patients undergoing stereotactic procedures for essential tremor received microinjections of muscimol (a γ‐aminobutyric acid‐A [GABA_A] agonist) into the ventralis intermedius thalamus in areas where tremor‐synchronous cells were identified electrophysiologically with microelectrode recordings and where tremor reduction occurred with electrical microstimulation. Injections of muscimol but not saline consistently reduced tremor in each patient. The effect had a mean latency of 7 minutes and lasted an average of 9 minutes. We propose that GABA‐mediated thalamic neuronal inhibition may represent a mechanism underlying the effectiveness of surgery for tremor and that GABA analogues could potentially be used therapeutically. Ann Neurol 1999;46:249–252