1. A marked rise in blood succinate was shown to occur in severely hypoxic patients.
2. A similar effect could be produced in the perfusate of the isolated perfused canine liver subjected to hypoxic hypoxia; in addition, tissue concentrations of succinate in the perfused liver progressively rose during hypoxia.
3. The elevation of succinate concentrations during hypoxia is partly due to reversal of the oxidative pathway from succinate to oxaloacetate.
4. A permeability barrier to succinate and fumarate exists between their locations within the cell and the circulation.
5. The permeability barrier to succinate but not to fumarate is broken down during hypoxia.