Plasma fatty acid profiles of 33 critically ill surgical patients receiving fat-free parenteral nutrition were examined at weekly intervals up to 28 days. While plasma total fatty acid concentration remained relatively constant and within the normal range, marked compositional alterations were apparent. Levels of linoleate (18:2ω6), the major essential fatty acid in man, fell below normal values (754 ± 259 μg/ml) in 67 percent of patients within 1 week after cessation of oral intake. Decreases in other ω6 unsaturated fatty acids, derived from linoleate, were also apparent. In contrast, gradual increases were observed in levels of endogenously synthesized fatty acids, palmitate (16:0), palmitoleate (16:1) and oleate (18:1ω9). A fatty acid unique to essential fatty acid deficiency, 5,8,11 eicosatrienoate (20:3ω9), appeared in 25 percent of the patients during the first week and in all patients by the third week of study. Considering the rapid appearance and progression of these bio-chemical changes, early initiation of linoleate supplementation appears justified to forestall the development of related clinical sequelae.