Albino rats of Wistar strain were subcutaneously injected with mercazole (1-methyl-2-mercaptoimidazol) 2.5mg/day for 7 to 35 days, orally administered on free demand with 0.05% mercazole solution for 70-300 days, and subcutaneously administered with D. L.-thyroxine 10γ/day for 14 to 28 days, 30γ/day for 14 days respectively. The histological alterations were observed in thyroid glands of control and experimental animals. The organ-body weight ratio of thyroid gland was elevated by the administration of mercazole in spite of the dropped ratio by thyroxine. According to the complete serial sections in thyroid glands, comprehending their adhering tissues and neighboring organs, in three normal rats, it was able to be determined that there were neither destructions of follicles nor desquamation of gland cells followed by the colloid reduction in follicular lumina, although these degenerating or destructing signs would be constantly much or less found at the outer parts of thyroid glands upon a common preparation of the gland conventionally removed at autopsy. Following the administration of mercazole, the follicles became in general smaller, irregularly shaped; the gland cells were ellongated, contained abundant mitochondria instead of PAS-positive granules.The activity of apocrine secretion was prevented apparently by the chemicals, notwithstanding the occurence of various number of tiny vacuoles with the uniform size at the supranuclear regions. These vacuoles might be eliminated through the striated border-like structures newly formed on the free surface of the gland cells into the lumina, where being tranformed into circumference vacuoles which thereafter increased in number and size to fill the lumina. Otherwise, by the persistent oral introduction of mercazole, enormous gross faintly stained colloid substances, associated with the huge vacuoles seemingly resulted from their liquefaction, often appeared at the basal parts of many gland cells.The proliferation of follicles induced by mercazole was in a state of equilibrium with the advancing amount of the chemicals; it was initiated with a dominance in quantity of the common gland cells, followed by the plump formation which bulged like nodules into the interspace, with a consequent separation from the mother follicles by the intrusions of blood vessels at the constricted part of the plump. The nodules were provided with some pseudofollicles, whose colloid increased in amount to occupy the developing real follicular lumina. It was not apparent to discriminate a parafollicular cell from a common gland cell in mercazole administered rats.By the injections of thyroxine, the follicles composed of flattened gland cells were either large or small with irregular shapes. In their cytoplasm mitochondria and secretory granules were either scanty or almost disappeared; the cytoplasmic projections showing an apocrine secretion, as well as circumference vacuoles, were rarely seen; the lumina of follicles were full of deeply stained colloid substances. Whereas the parafollicular cells hypertrophied and were in hyperplasia that they arranged themselves compactly but confusedly to wholly mantle the atrophic follicles with extraordinarily flattened gland cells, and in their cytoplasm there were observed a number of vacuoles or PAS-positive granules concurrently stained with iron hematoxylin. Above alterations were augmented with increasing dosage of in fused thyroxine. This paper deals with a role of parafollicular cells in both metabolic and growth activties in thyroid gland and some links to their humoral control were discussed. The administrations of mercazole or thyroxine fairly caused to promote or prevent the release of TSH from the anterior lobe of the pituitary respectively, and in approaching the morphological response to the chemicals