Lipid emulsions used in parenteral nutrition are prone to peroxidation that may be an important feature of oxygen-associated tissue damage. Incubation of lipid emulsion [Intralipid (IL)] with H2O2 and FeCl2 increased lipid peroxidation, measurable as increased production of pentane, from 0.39 +/- 0.33 to 0.99 +/- 0.18 microM (p less than 0.0001). Malondialdehyde was increased from 0.010 +/- 0.005 mM to 0.380 +/- 0.025 mM (p less than 0.001). Superoxide dismutase and catalase (each 100 U/mL) or vitamin C (10 mM) inhibited pentane and malondialdehyde production (p less than 0.0001). Incubation of human erythrocytes in the presence of FeCl2 caused 11.0 +/- 3.2% hemolysis (control 0.95 +/- 0.14%). Addition of 0.44% IL increased hemolysis to 66.5 +/- 3.4%, whereas further addition of vitamin E or C significantly inhibited hemolysis to 16.4 +/- 8.1 and 38.9 +/- 7.1%, respectively (p less than 0.0001). IL was administered i.v. to eight preterm infants. It increased 3- to 28-fold (p less than 0.001) the amount of pentane in expired breath. Partly, this increase was due to pentane dissolved in IL as a result of lipid peroxidation during storage. After discontinuing IL infusion, the elimination of pentane was nonexponential, consisting of a rapid and a slow component. According to our results, IL undergoes peroxidation causing free-radical-dependent damage to human cells. We propose that the adverse effects of parenteral IL are partially caused by free oxygen radicals generated by lipid peroxidation.