The mechanism of chronic cholestasis observed during prolonged parenteral nutrition remains unclear. We studied liver function tests in 18 consecutive gastroenterological adult patients submitted to 18 mo (median; range 6-66 mo) of parenteral nutrition. Seven patients (group B) developed a cholestatic nonobstructive jaundice, culminating after 3 mo, (1-4 mo) whereas 11 patients (group A) did not develop chronic abnormalities on liver function tests during parenteral nutrition. Liver biopsies obtained at 4 mo (3-6 mo) in 6 group B patients demonstrated bile duct proliferation in the portal area, with extensive fibrosis, cholestasis, and focal necrosis of hepatocytes. Initial intakes of calories, fat, and protein were higher (p less than 0.01) in group B than in group A patients and, when reduced, were associated with reversal of jaundice and improvement in liver function tests and histological findings. These data suggest that the development and course of cholestasis are influenced by excess parenteral intake of protein and mixed-energy sources.