In order to determine whether the adrenal glands play a primary or secondary role in the pathogenesis of the spontaneous arteriosclerosis which occurs in repeatedly bred rats, sexually mature female, Sprague-Dawley rats were adrenalectomized and maintained during four successive pregnancies. Some of the breeders were treated with deoxycorticosterone (DOCA) and 0.5% saline. The adrenalectomized breeders did not develop arteriosclerosis, beta cell degranulations, or those which has accesory or regenerated adrenal glandular tissue. Surprisingly, intact DOCA-treated breeders also showed inhibition of arterial disease but they did have fatty livers and beta cell degranulation. Body and organ weights, serum enzymes, lipids, glucose, BUN, and corticosterone were elevated in breeder rats but not to such high levels as is usual in repeatedly bred rats. These findings demonstrate that the presence of the adrenal glands is essential for the pathogenesis of the spontaneous arteriosclerosis, fatty liver, and beta cell degranulation which occurs in repeatedly bred, female rats.