Among the factors that can govern the relative rates of mitochondrial oxidation of isocitrate by means of the isocitrate dehydrogenases linked to diphospho-and triphosphopyridine nucleotides are the intramitochondrial concentrations of these nucleotides. Yeast mitochondria contain enzymes that can alter the ratio of these pyridine nucleotides by interconverting them. A diphosphopyridine nucleotide kinase catalyzes the formation of triphosphopyridine nucleotide from diphosphopyridine nucleotide and adenosine triphosphate; a phosphatase converts triphosphopyridine nucleotide to diphosphopyridine nucleotide. Both reactions are more active with the reduced forms of the pyridine nucleotide coenzymes. These studies suggest that the activity of the mitochondrial triphosphopyridine-nucleotide-linked isocitrate dehydrogenase may be regulated by a cyclic system of pyridine-nucleotide interconversions involving triphosphopyridine nucleotide synthesis and breakdown.