AbstractThe effect of moderate hypoxia (50.5 kPa air) and severe hypoxia (40.8 kPa air)in vivoon liver and heart triglyceride concentration and mitochondrial respiration rates was studied. Liver triglyceride concentrations increased in severe hypoxia from 7.3 μmol/g wet weight to 23.3 μmol/g wet weight over 7 days. After the period of seven days in severe hypoxia, the palmitate, octanoate and palmitoylcarnitine oxidation rates of mitochondrial suspensions were significantly reduced when the citric acid cycle was operative. No decrease in the fatty acid, fatty acyl‐CoA or carnitine derivative oxidation was observed when only the β oxidation system was studied. Mitochondria isolated from the heart or liver after seven days in severe hypoxia showed reduced respiratory control ratios, the decrease being from the normal 4.9 to 1.9 in the liver mitochondria using succinate as substrate. The reduction in respiratory control was mainly due to lowered State 3 respiration rates. Some reduction in the ratio was also observed in the fasting controls, from 5.8 to 3.4 with succinate. The respiratory control ratio could be partially normalized by the addition of albumin to the isolation medium for the liver mitochondria after severe hypoxia. Under these conditions, however, the State 4 respiration of the mitochondria from the hypoxic animals was higher than that for the cont