1. Adrenal glands of guinea-pigs with avitaminosis-C and hypovitaminosis-C were examined and compared with those of normal controls fed on diets containing ascorbic acid as well as with pair-fed controls kept on restricted food intakes. Guinea-pigs with avitaminosis-C were also injected with either adrenocorticotrophic hormone (ACTH) or cortisone and compared with normal controls or pair-fed controls similarly injected.
2. Adrenals of animals with avitaminosis-C increased in absolute (20%) and relative weight (120%). The number of mitoses increased fourfold in the middle stage and tenfold in the terminal stage of the deficiency. The zona fasciculata contained many lipid-free, hyperplastic and dividing cells. Cortisone prevented the increase in weight and in mitoses and also the histological changes. Administration of ACTH to guinea-pigs with early avitaminosis increased the mitoses fourfold, but when given to normal guinea-pigs mitoses increased sevenfold. Histological changes were similar to those seen in advanced avitaminosis.
3. In the adrenals of animals with hypovitaminosis-C, neither the absolute weight nor the number of mitoses were greater than normal but the relative weight of the glands was doubled.
4. It is concluded that the increase in adrenal weight which occurred in avitaminosis-C was the result of a hyperplastic response to high levels of endogenous ACTH known to be present in the blood of deficient animals.