The effects of a conventional 1000 kcal diet, and of a further restriction of dietary fat by a fat substitute, on the concentrations of vitamin A and E in plasma and LDL, the formation of lipid peroxides and eicosanoids were investigated in 10 obese volunteers. In vitro copper catalyzed oxidation of conjugated dienes, lipid peroxides and TBARS activity, measured in LDL samples after week 2 (supplementation with 140 mg/d alpha-tocopherol and 5000 IU retinol-acetat for two weeks), week 6 (conventional diet) and week 10 (fat substitute), increased with vitamin E depletion statistically significant after week 10 compared to the values after week 2. Concomitantly, PGE2 and LTB4, determined by RIA, increased to 344% and 166%, respectively, compared to the values after week 2. PGM, determined as tetranorprostanedioic acid by GC-MS, increased to 120%. Stimulation of lipid peroxidation and eicosanoid formation was more pronounced in persons with initially low (19 - 26 micromol/l plasma) than in those with high (37 - 70 pmol/l plasma) concentrations of alpha-tocopherol. We conclude that fat restricted diets can lead to an unwanted stimulation of lipid peroxidation and eicosanoid formation, which may be relevant in states of disease, e. g. arteriosclerosis or rheumatoid arthritis.