Peroxidation of endogenous lipid by rat liver microsomes, coupled with oxidation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) was markedly stimulated in the presence of indomethacin [1-(p-chlorobenzyl)-5-methoxy-2-methyl-3-indole acetic acid], a potent anti-inflammatory drug. This system also generated a rapidly developed chemiluminescense (CL), the intensity and rate of development of which were related to indomethacin concentration and the amount of peroxidation in the sample. Microsomes from rats fed a liquid diet based on Sego diet drink (Pet Incorporated) failed to chemiluminesce with or without added indomethacin. Supplementation of the Sego diet with a polyunsaturated fatty acid (C18:3) did not restore the chemiluminescense. In vitro and in vivo studies indicate that vitamin E (a component of the Sego liquid diet) inhibited the microsomal chemiluminescense reaction in a dose related manner.