Streptozotocin diabetes in rats is associated with reduced function of the hypothalamo-pituitary-thyroid axis. The structure and hormone secretion of the thyroid and pituitary glands were studied in adult male rats 1 month after streptozotocin injection. The thyroid of diabetic rats was characterized by decreased follicle area and epithelial thickness. By electron microscopy, thyroid epithelial cells were characterized by flattened and almost empty rough endoplasmic reticulum cisternae, scanty exocytotic apical and endocytotic vesicles as well as degenerate mitochondria and rough endoplasmic reticulum. By immunohistochemistry, intracolloidal thyroglobulin and T3 as well as intraepithelial thyroglobulin were reduced. Electron microscopic and immunohistochemical analysis of pituitary glands showed that in diabetic rats thyrotrophs were mostly of type II, and the number of thyrotrophs (type I + type II) was greater than in controls. By radioimmunoassay (RIA), plasma T3, T4, and TSH levels were markedly reduced, and the TSH response to TRH was deficient in diabetic animals. The pituitary TSH concentration was increased, as expected from the morphological data. This study demonstrates severe structural changes in the thyroid and pituitary glands of diabetic rats which are accompanied by marked alterations of their secretory activity.