Abstract A novel form of allosteric control in which NAD-specific glutamic dehydrogenases obtained from taxonomically related fungi are activated by NADP+, NADPH, and P-enolpyruvate has been elucidated. Citrate and isocitrate are equally effective as inhibitors of the enzymes. The enzymes are allosterically inhibited by their substrates, α-ketoglutarate and ammonia, in a highly cooperative manner. NADP+, NADPH, and P-enolpyruvate antagonize substrate inhibition. These activators also function as multivalent modulators in releasing the enzyme from inhibition by citrate. Control of the enzyme activity is unidirectionally oriented such that it is the reductive amination that is effectively controlled. The purified glutamic dehydrogenases have a molecular weight of 225,000 daltons. They are susceptible to inactivation by hydrodynamic shear in sucrose density gradients at alkaline pH levels. Inactivation by sedimentation can be prevented by bound activators. Inactivation and dissociation of the enzyme are related phenomena. Synthesis of the glutamic dehydrogenases can be repressed by addition of glucose to the growth medium. Glutamate acts as an inducer. NADP-specific isocitric dehydrogenase present in these fungi responds in the opposite manner to the metabolism of glucose and glutamate.