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The development of new treatments for essential tremor, the most frequent movement disorder, is limited by a poor understanding of its pathophysiology and the relative paucity of clinicopathological studies. Here, we report a post-mortem decrease in GABA_A (35% reduction) and GABA_B (22–31% reduction) receptors in the dentate nucleus of the cerebellum from individuals with essential tremor, compared with controls or individuals with Parkinson's disease, as assessed by receptor-binding autoradiography. Concentrations of GABA_B receptors in the dentate nucleus were inversely correlated with the duration of essential tremor symptoms (r² = 0.44, P < 0.05), suggesting that the loss of GABA_B receptors follows the progression of the disease. In situ hybridization experiments also revealed a diminution of GABA_B(1a+b) receptor messenger RNA in essential tremor (↓27%). In contrast, no significant …