This study investigated the etiology of fat infiltration of the liver during total parenteral nutrition. We measured the content of liver lipids, serum lipids, liver lipogenic enzymes, rates of in vivo fatty acid synthesis, and carcass composition in rats during continuous intravenous (iv) and intragastric (ig) feeding of two diets containing either 100% glucose or 75% glucose-25% lipid (20% Intralipid). Two groups of orally (O) fed rats were given solid diets similar to either the glucose or glucose-lipid solution in energy and nitrogen content. All six groups of rats (285-295 g) received 230 kcal X kg-1 X day -1 and 766 mg N X kg-1 X day-1. Total liver fat was greater after feeding the glucose diet ig rather than iv. However, feeding the glucose-lipid diet ig but not iv reduced the accumulation of liver fat by 49%. There were no differences in serum glucose concentrations among the three groups fed the glucose solution. Serum glucose concentrations in iv and O rats fed either diet were not significantly different; whereas feeding the glucose-lipid solution ig lowered serum glucose compared with the 100% glucose solution. Insulin concentrations were similar among all groups. The concentrations of serum triglycerides and cholesterol were higher in the groups fed the glucose-lipid diet. The activities of the liver lipogenic enzymes and rates of fatty acid synthesis were higher in iv- and ig-fed rats receiving the glucose diet compared with the glucose-lipid diet.(ABSTRACT TRUNCATED AT 250 WORDS)