The original source of thyroidectomy cells (TX-cells) in rats was investigated electron microscopically. Thyrotrophs did not respond so definitely to thyroidectomy as gonadotrophs did to castration. In thyrotrophs, changes in terms of hyperplasia, hypertrophy and de-or hypergranulation were not manifested. There was no evidence that TX-cells belonged to hyperactive thyrotrophs. The course of transformation from the degranulated acidophils to TX-cells was clearly demonstrated in sequence in this study. Hypertrophy, deformation of the cell, expansion of cisternae, occurrence of intracisternal granules and enlargement of the Golgi-ring, these were manifestations of the developmental process of degranulated acidophils into TX-cells. The other process of transformation of acidophils into TX-cells seemed related to the gradual dilation of ER without discharging their large granules completely. During the chronic phase of thyroidectomy, the anterior pituitaries were filled with TX-cells and their precursors. High vesiculation could be considered as an intrinsic biological reaction which is commonly seen in most of hypophyseal cells during thyroxine deficiency. It was, therefore, suggested that degranulated or slightly granulated acidophils might be predominantly the original sources of TX-cells. Thus, the acidophil theory has been firmly established as to the genesis of TX-cells. We, at the same time, wanted to open up a possibility that some TX-cells might arise from immature basophils, but the valid evidence was not produced in this study. It was verified electron microscopically that the fully developed round TX-cells seemingly like signet-ring-typed castration cells were quite different from genuine castration cells, although both cells had the same staining properties and light microscopical characteristics. However, a number of immature gonadotrophs came into being during the chronic phase of thyroidectomy.