Background The effects of chronic hypoxia on cardiac membrane fatty acids and on lipid peroxidation were examined, as well as the effect of l-carnitine (LCAR), which suppresses lipid peroxidation, on this process. Methods and Results Four-week-old Sprague-Dawley rats were exposed to 10% oxygen for 14 days ("Hypoxia"), and then to 100% oxygen for 12 h (O₂). LCAR (200 mg/kg) was administered by intraperitoneal injection daily for 2 weeks. Fatty acid composition, malondialdehyde (MDA) as a lipid peroxidation product, and antioxidants (superoxide dismutase (SOD), glutathione peroxidase and catalase) were measured. The concentration of linoleic acid was lower, and that of docosahexaenoic acid, which has more double bonds than linoleic acid, was increased in hypoxic hearts. SOD activity decreased in hypoxia, whereas MDA was unchanged, but significantly increased in "Hypoxia"+O₂. LCAR reduced the increase in MDA, and had no effect on SOD activity or fatty acid composition. The administration of LCAR caused an increase in the ventricular levels of acetylcarnitine. Conclusions These results suggest that chronic hypoxia changes the cardiac fatty acid composition of juvenile rats to fatty acids that contain more double-bonds and reduce SOD activity, and that lipid peroxidation was augmented by exposure to oxygen. (Circ J 2008; 72: 1359 - 1366)