Magnocellular neurons in the cholinergic nucleus basalis appear to be vulnerable in a variety of pathological conditions, including chronic alcoholism. While neurofibrillary degeneration of these neurons has been noted in a number of disorders characterized by dementia, the mechanism of cell death in thiamine-deficient chronic alcoholics has not been identified. In the present post-mortem investigation, multiple brain regions of seven thiamine-deficient chronic alcoholics, three neurologically asymptomatic chronic alcoholics and seven non-alcoholic age matched controls were screened for neurofibrillary pathology using both tau-immunohistochemistry and a modified Bielschowsky silver stain. In chronic alcoholics with thiamine deficiency, neurofibrillary pathology was found in the nucleus basalis, but not any other brain region. Neurofibrillary tangles were not seen in age-matched controls and were infrequent in alcoholics without neuropathological signs of thiamine-deficiency. Neurofibrillary tangles were most numerous in those cases with cell loss in the nucleus basalis. These findings suggest that neurodegeneration of the nucleus basalis in chronic alcoholics proceeds through the formation of neurofibrillary tangles.