Overt hepatic encephalopathy precipitated by zinc deficiency. Encephalopathy in liver disease may be unresponsive to protein restriction, lactulose, and neomycin. Zinc supplements have been reported to improve psychometric performance in liver cirrhosis, but the importance of zinc deficiency in overt hepatic encephalopathy has not yet been clearly established. A patient with severe recurrent hepatic encephalopathy was studied to determine the relation between her signs of encephalopathy and zinc deficiency. The study included a period in which zinc deficiency was artificially induced by oral histidine. An episode of overt encephalopathy occurred that was identical to earlier episodes and responded to oral zinc. The study showed an association between encephalopathy and zinc deficiency by successive zinc depletion and supplementation regimens. Long-term zinc supplementation improved severe recurrent hepatic encephalopathy and therefore the quality of life. 