NMRI mice were fed diets supplemented with 0.05, 0.2, or 2% (w/w) docosahexaenoic acid (DHA), a polyunsaturated fatty acid present in fish oil, for 3 d, 3 wk, or 3 mon. The doses of DHA were chosen to supply the mice with concentrations of DHA which approximate those that have been reported to be beneficial to patients with peroxisomal disease. Diets containing 0.05 or 0.2% DHA did not change hepatic, myocardial, and renal catalase (EC 188.8.131.52) activity except for a slight but significant increase (to 120%) in myocardial catalase activity in mice treated with the 0.05% DHA diet for 3 mon. A diet with 2% DHA induced myocardia[ catalase activity to 150% after both 3 d and 3 wk of administration. In the liver of mice fed this diet for 3 wk, hepatic catalase activity was increased to 140% while no induction of palmitoyl-CoA oxidase (EC 184.108.40.206), urate oxidase (EC 220.127.116.11), and L-alpha-hydroxyisovalerate oxidase (EC 1.1.3.a) was observed. With the light microscope, no changes in peroxisomal morphology were visually evaluated in catalase stained sections of liver, myocardium, and kidney of mice fed either diet. Our results show that in healthy mice a low dietary DHA dose (<0.2%; this corresponds to a dose prescribed to peroxisomal patients) has no effect on several hepatic peroxisomal H2O2-producing enzymes, including the rate-limiting enzyme of the peroxisomal fatty acid P-oxidation. This may indicate that such a DHA dose will not add a strong load on the often disturbed fatty acid metabolism in the liver of patients with peroxisomal disorders.