Adrenalectomy of 8- to 9-week old Sprague-Dawley rats produced decreases in the levels of glutamate dehydrogenase (GDH). Administration of cortisol hemisuccinate (100 ng/g BW) resulted in a transient increase in the level of the enzyme; on low or zero protein diets, this response continued for much longer periods of time. In adrenalectomized animals, induction by (Bu)2cAMP could be seen, but only in conjunction with cortisol, which exerted a permissive effect. In thyroidectomized animals, the level of GDH was not lowered significantly, but was increased by T3 (5-40 ng/g BW). The response was bimodal with time, showing a peak of activity at 2 h, and a second peak at 16 h. The first peak was not inhibited by actinomycin D or by cycloheximide, and was not associated with increased incorporation of 3H-leucine into immunoprecipitable GDH. The second peak was inhibited by both antibiotics, and was associated with increased incorporation of labeled leucine into the enzyme. It appears therefore that thyroid hormones exert two separate effects on GDH, the first one not involving de novo synthesis of enzyme protein and the other involving de novo synthesis. The turnover of GDH appeared to be unaffected by thyroidectomy. In animals which were both adrenalectomized and thyroidectomized, cortisol and T3 were able to produce induction of GDH, indicating the absence of any permissive effects between the two.