The effects of an intravenously administered lipid emulsion supplemented with gamma-linolenic acid on the fatty acid profile of premature infants were compared with those of two conventional lipid emulsions. Fifty-nine premature neonates receiving total parenteral nutrition were randomly assigned to receive either fat emulsion containing gamma-linolenic acid and long-chain triglycerides (LCT), an LCT emulsion, or a 50% (wt/wt) mixture of medium-chain triglycerides and LCT emulsion. Forty-nine infants completed the study. During the 6-day study there was a significant tenfold increase in the plasma levels of gamma-linoleic acid in the supplemented group versus the other two groups. A significant threefold to fivefold increase in the omega 6 long-chain polyunsaturated fatty acids was observed in all groups. These changes seemed to be attributable mostly to linoleic acid from the lipid emulsion, despite the 50% lower dose in the medium- and long-chain triglycerides group. The increase in the omega 3 long-chain polyunsaturated fatty acids also was mainly caused by a similar increase in the level of alpha-linolenic acid. No differences were recorded in the linoleic/alpha-linolenic acid ratio among the groups. Plasma levels of some of the semiessential fatty acids were significantly higher in the medium- and long-chain triglycerides group than in the LCT group. This may be related to slower elimination of LCT, to the difference between emulsions, or to less substrate inhibition on delta-6-desaturase, which seems to be less of a rate-limiting enzyme than previously considered. Further intravenous feeding trials are needed to identify the optimal balance of fatty acids for nutrition of these premature infants.