Activities of thiamine monophosphatase (TMPase) and thiamine diphosphatase (TDPase) were measured in homogenates of brain tissue obtained at autopsy from eight alcoholic cirrhotic patients who died in hepatic coma and nine controls matched for age and for postmortem delay interval and free from neurological or psychiatric disorders, hepatic disease, or other conditions of grossly impaired nutritional status. Enzyme activities were measured by standard spectrophotometric techniques. Both TMPase and TDPase were distributed unevenly in brain with highest activities being recorded in temporal cortex. Regional correlations between TMPase and TDPase, however, were poor. TDPase activities in brain tissue from alcoholic cirrhotic patients were significantly increased in 5 of 6 brain regions, by 26 to 153% (p < 0.05). TMPase activities in alcoholic cirrhotics, on the other hand, were unchanged in all brain regions, with the exception of caudate nucleus where they were increased by 70% (p < 0.05). These findings add to the substantial body of evidence suggesting that alcoholic liver disease is associated with abnormal thiamine status and with altered thiamine neurochemistry. Increased TDP degradation resulting from increased activities of TDPase could contribute to the pathophysiological mechanisms involved in alcohol-related brain dysfunction.