The non-neoplastic and neoplastic lesions in adrenals, thyroids, pituitary, uterus, ovaries, testes and mammary gland of senile untreated Sprague-Dawley rats were evaluated. The correlation between the neoplastic and non-neoplastic lesions in the pituitary gland and those in the target organs was made. The pituitary gland of the senile Sprague-Dawley rats had focal or diffuse hyperplasia and/or hypertrophy of PRL, STH, and ACTH cells. Approximately 47% of the males and 62% of the females had pituitary adenomas. Multiple adenomas in the same pituitary were noted in 7% of the males and in 11% of the females. Although many adenomas contained pleomorphic foci and quite a number of mitotic figures and were locally invasive, no evidence of distant metastases was discovered; therefore carcinoma was not diagnosed in the present material. The adenomas observed were divided into different types on the basis of the cytological characteristics of the cellular elements. Single cell-type adenomas such as PRL-, ACTH-, STH-, TSH-, immature- gonadotrophin-cell adenomas, and mixed cell (more than one cell type) adenomas were diagnosed. The adenomas containing PRL cells were the predominant type of neoplasms and they represented 30% and 34% of the total pituitary neoplastic lesions observed in males and females, respectively. The cytological changes in the hypophyseal cell types in senile Sprague-Dawley rats were usually accompanied by spontaneous non-neoplastic and neoplastic lesions in adrenals, thyroids, testes, ovaries, and mammary gland. The possible role of the hypophyseal hormones in the induction of the non-neoplastic and neoplastic lesions in the target organs is discussed. The combination of the spontaneous endocrine tumors could be associated both with aging and with genetic background of the animals. In addition, this polyglandular proliferative lesion in Sprague-Dawley rats might represent a potential model of mixed MEN syndrome.