The changes induced in the lymph-node post-capillary venules of male and female mice, 1, 2, 4, 7, 10 and 14 days after oestrogen administration were studied in 1 micron sections and with the electron microscope. The endothelial cells of the post-capillary venules are higher in female than in male control mice. On the first and second days after Hexoestrol administration there is an increase in the number of ribosomes and polyribosomes lying free in the cytoplasm of the endothelial cells. These cells were significantly increased in height between day 2 and day 7, in both male and female Hexoestrol-receiving mice, remaining at high levels thereafter. The increase in height was accompanied by an increase in the Golgi elements which occupied the major part of the cytoplasm of the endothelial cells. Lysosomes, multivesicular bodies and signs of phagocytosis were more often seen. In contrast, the numbers of lymphocytes passing through the post-capillary venule wall were significantly decreased, probably due to a direct effect of Hexoestrol on the thymus. The relation of an oestrogenic effect on the ultrastructure of the post-capillary venules to the sex differences seen in the immune response is discussed. The possibility that this may constitute a part of a general oestrogenic effect on the reticuloendothelial system is also considered.