The prevention of essential fatty acid deficiency and the provision of adequate amounts of energy are two major concerns in total parenteral nutrition. Since earlier preparations of fat emulsion used to supplement the usual regimen of hypertonic glucose and amino acids have widely varying clinical acceptability, a new product, a safflower oil emulsion available in two concentrations (Liposyn), was evaluated. In four clinical trials the emulsion was used as a supplement to total parenteral nutrition. In five surgical patients 500 ml of the 10% emulsion infused every third day prevented or corrected essential fatty acid deficiency; however, in some cases in infusion every other day may be necessary. In 40 patients in severe catabolic states the emulsion provided 30% to 50% of the energy required daily: 10 patients received the 10% emulsion for 14 to 42 days, 9 patients received each emulsion in turn for 7 days, and 21 patient received the 20% emulsion for 14 to 28 days. All the patients survived and tolerated the lipid well; no adverse clinical effects were attributable to the lipid infusions. Transient mild, apparently clinically insignificant abnormalities in the results of one or more liver function tests and eosinophilia were observed in some patients. Thus, the safflower oil emulsion, at both concentrations, was safe and effective as a source of 30% to 50% of the energy required daily by seriously ill patients.