The object of this review is not to present a detailed historical survey of the subject of hepatic coma, nor to attempt to elucidate all the varied biological and biochemical phenomena that have been recorded to date in human, experimental, and in vitro investigations on this subject, but rather to formulate a discussion and an appraisal of the more recent and salient observations in the field. While the danger of extrapolating the data gathered from in vitro and from experimental studies to the human disorder is recognized, all sources of relevant and related information have been utilized. It has not been thought desirable to consider the pathogenesis of the coma separately in the different types of liver disease (e.g., acute hepatic necrosis, portal cirrhosis, and by-passing of the liver by shunts), but to explore the possible mechanisms leading up to the neurological manifestations—and especially to the change in the state