Vitamin E and essential fatty acid status were examined in two groups of patients, one receiving fat-free total parenteral nutrition (TPN) with intravenous all-rac-alpha-tocopherol for vitamin E deficiency and the other receiving routine intravenous fat (Intralipid, 10%) emulsions with TPN to supply both fatty acid and vitamin E requirements. Initial evaluation of both groups revealed a 50% incidence of vitamin E deficiency, platelet hyperaggregation, or in vitro H2O2-induced hemolysis. Only platelet hyperaggregation correlated significantly with vitamin E deficiency. Supplementation with all-rac-alpha-tocopherol corrected platelet hyperaggregation and H2O2-induced hemolysis; daily dosage requirements of 25-50 mg (fat-free TPN) or more (with intravenous fat) suggest increased vitamin E requirements during TPN. Intravenous fat emulsion did not correct the platelet and red blood cell abnormalities, a result of either increased vitamin E requirements or low alpha-tocopherol-equivalent content of the emulsion. Essential fatty acid deficiency (EFAD) was observed in seven patients with an associated platelet hyperaggregation independent of vitamin E deficiency. Prolonged TPN for enterocutaneous fistulae in three patients was associated with persistent EFAD and platelet hyperaggregation despite up to 2.0 liters of intravenous fat emulsion weekly.