The morphologic effects of estrogen withdrawal from an estrogen-dependent tumor were investigated using light and electron microscopy. Twenty-five male hooded rats received interscapular implants of an estrogen-induced, estrogen-dependent adrenocortical tumor as well as subcutaneous estrone pellets. The tumors were examined when they had reached one and two centimeters in size. The pellets were removed from a second group and the tumors examined when they had decreased to a minimum size. A third group received a second pellet after the tumor had regressed to a minimum size following removal of the first pellet. The primary tumors were characterized by plump, active-looking cells growing usually in a sheet-like pattern. The ultrastructural features of these tumors included large, bizarre mitochondria with tubular cristae, prominent polyribosomal aggregates and Golgi zones as well as fairly frequent centrioles. The regressing tumors consisted of smaller cells growing in a trabecular pattern and heavily infiltrated with eosinophils. The fine structure of the tumor cells consisted of small mitochondria with a dense matrix and a few irregular cristae. Myelin figures and residual bodies were present in significant numbers only in the regressing tumors while (primary)lysosomes were more frequent in the growing tumors. The tumors examined after reimplantation of estrone showed features of the primary growth tumors plus residual foci of regression. It thus appears that estrogen acts as a trophic factor for this experimental tumor much as it does for the uterus. Tumor cells can survive in its absence, but require it for growth. The ultrastructural expression of estrogen administration seen in this study is the proliferation of mitochondria as an energy source and polyribosomes for the production of proteins for endogenous consumption. The removal of estrogen results in a generalized reduction in cellular activity and an accumulation of the products of autophagy. Further work is required to tie in these results with the studies being done on the basic mechanisms of estrogen action at the level of molecular biology. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate