We evaluated the effect of total parenteral nutrition (TPN) on abnormalities of hepatic histology. Liver biopsies of 93 patients who were concurrently receiving TPN were compared with a control group of 35 patients. The control patients were matched for extent of preexisting liver disease and degree of illness. The liver biopsy specimens were blindly graded on 19 histopathologic findings, including fatty change, portal inflammation, and cholestasis. Twenty-seven clinical variables, such as preexisting liver disease, the presence or absence of sepsis or shock, and number of days receiving TPN before biopsy, were recorded. Individual and partial correlations were established between the clinical variables and histopathologic findings. The control and TPN groups proved to have been closely matched regarding the extent of risk factors for hepatic histopathologic features. Positive correlations were repeatedly found between abnormal hepatic histologic features and preexisting liver disease, abdominal sepsis, renal failure, and blood transfusion but not with the administration of TPN. We conclude that clinical phenomena, such as existing liver disease, renal failure, and abdominal sepsis, rather than administration of TPN, had a predominant effect on histopathologic features in this group of patients.