1. 1. The NAD +-specific isocitrate dehydrogenase ( l s-isocitrate:NAD + oxido-reductase (decarboxylating), EC 1.1.1.41) from baker's yeast is inhibited competitively by certain anions. AMP counteracts this inhibition. 2. 2. The enzyme is also inhibited by the substrate isocitrate. This inhibition appears to be due to the removal of the cofactor Mg 2+ by the formation of an isocitrate complex. 3. 3. Kinetic experiments, at pH 7.6, have shown that the order of the reaction with respect to isocitrate is decreased by AMP from about 3 to 1.5. 4. 4. The order of the reaction with respect to Mg 2+ is increased from 1 to 2 by the addition of KCl, and restored to 1 by AMP. 5. 5. It is suggested that the addition of isocitrate and Mg 2+ to the enzyme may be random, and the possibility is discussed that the occurence of a random mechanism for the addition of the reactants may explain the kinetic behavior of the enzyme.