Rapid involution of the thymus was induced in SD rats after administration of high-dose estradiol benzoate. The prominent histological changes observed were as follows: (1) the thymic cortex was become thinner; (2) the corticomedullary ratio was decreased; and (3) a substantial loss of cortical lymphocytes occurred. As a consequence, marked reduction in thymus weight was caused. Under electron microscope, the epithelial reticular cells (ERCs) were found, to be a heterogenous cell group. Their responses to high-dose estradiol were different from each other, and the distinctive changes observed were: (1) cell degeneration changes in some pale ERCs were observed; (2) the other pale ERCs were found to be filled with lower density vacuoles which were very similar to secretory vacuoles; and (3) the dark ERCs were inereased obviously, and many collagen fibril bundles were seen in the vicinity of their perikarya or wrapped by their cytoplasmic processes. There were no striking ultrastructural changes in thymocytes. However, the number of ANAE positive cells in the experimental group was lower than that of the controls evidently. In addition, a large number of plasma cells were observed in the cortex of the experimental group. Based on the above mentioned observations, the possible mechanism of the estradiol effect on the thymus involution was discussed.