Positron emission tomography (PET) is a powerful and versatile tool for the investigation of hepatic encephalopathy (HE). This nuclear medicine imaging technique produces quantitative images of the distribution of a radiopharmaceutical at one or more times after its administration. Thus, PET images can be used as data in mathematical models of physiologically important processes, including cerebral blood flow, an index of neural activity, or glucose and ammonia metabolism. Using PET, we have demonstrated abnormalities in all of these processes in patients, even though many had only minimal HE. In HE patients we have found increases in the cerebral ammonia metabolic rate, because of hyperammonemia and an increase in the permeability of the blood-brain barrier to ammonia and abnormal patterns of blood flow and glucose metabolism. In a recent collaborative study, alterations in the resting glucose metabolic rate were found to have significant correlations with a variety of neuropsychological tests used to detect mild HE including Trailmaking A and B, symbol-digit, and other tests. Activation techniques have not yet been applied to map sites affected by HE, but recent data using the paced serial auditory addition test and an auditory continuous performance task have proven to be sensitive indicators in minimally impaired patients. The full potential of PET to evaluate neurotransmitter function is as yet unrealized.