I ntrahepatic proteolysis is a major determinant of secretion of ApoB-containing lipoproteins into plasma. Stimulation of post-ER presecretory proteolysis (PERPP) of ApoB by n-3 polyunsaturated fatty acids has been found to result in reduced secretion of VLDL particles by hepatocytes. A new study has shown that this stimulation is promoted by pro-oxidant conditions that result in increased hepatic lipid hydroperoxide content. Conversely, PERPP is suppressed by antioxidants and by saturated fatty acids, which are not susceptible to lipid peroxidation. Hence reduction of oxidative stress may have the unexpected side effect of increasing plasma lipid levels.