cf. CA 54, 14467i.Clin. use of diphenylhydantoin (I) is frequently accompanied by side effects, including hirsutism and gingival hyperplasia, which suggests the possibility of pituitary-adrenal stimulation.An attempt was made to verify this mechanism in the rat.Subcutaneous injection of 40 mg. I produced a 13% drop in adrenal ascorbic acid content, but a similar dose of 5,5-diphenyl-4-imidazolidinone (II) had no such effect.The same dose of I produced a 25-30% increase in the glycogen content of brain, muscle, and liver 4 hrs. after injection; however, 4 times that amount of II was almost without effect.At 40 mg./kg. I raised the electroshock threshold 12 and 14% in the hypophysectomized rat and the adrenalectomized rat, resp., compared to only 3% in the intact rat.At a much higher dose (1 g./kg.) II raised the resp. thresholds 20, 24, and 26%.In chronic experiments (40 mg./kg. twice per day for 12 days) I reduced thymus weight 25% and increased adrenal weight 40%, while II had no effect on thymus weight and increased adrenal weight 35%.I elevated plasma cortisone levels and II increased them to a greater extent.Plasma hydrocortisone was unaffected by I but slightly reduced by II.The thymus atrophy produced by I may be related to the relative higher hydrocortisone level than in animals treated with II.Six-day treatment with 40 mg./kg./day I increased the electroshock threshold 50% in hypophysectomized, 40% in adrenalectomized, and 20% in intact rats.A 4-fold greater dose of II resulted in a 30% augmentation of the threshold in all 3 groups of rats.It was concluded from these results that I stimulates the hypophyseal-adrenocortical system but that II is without effect on this system.