We examined the effect of long-chain triglyceride (LCT) and medium-chain triglyceride (MCT) emulsions on hepatic regeneration. After approximately 70% hepatectomy, Sprague-Dawley rats were maintained for 96 hours on total parenteral nutrition (TPN) (250 kcal/kg per day; nonprotein calories-nitrogen 160:1) with LCT or MCT as 30% of nonprotein calories. There were no significant differences in the body weight, cumulative nitrogen balance, urinary 3-methylhistidine excretion, or changes in the energy stores between the two groups; but the fatty acid composition of the phospholipid fraction of the regenerating liver differed significantly between the LCT and the MCT groups. The extent of hepatic regeneration by weight was 88.7 +/- 10.5% in the MCT group and 99.1 +/- 10.6% in the LCT group by 96 hours after hepatectomy. Furthermore, the incorporation of 3H-orotic acid into DNA and RNA of regenerating liver cells in the LCT group was higher than in the MCT group 24 hours after hepatectomy. These observations indicate that essential fatty acids--components of the cell membrane and precursors as functional mediators--are very important to hepatic regeneration.