The three segments (S1, S2, S3) of the proximal tubule of the rat kidney were investigated, with special reference to lysosomes, after castration, estradiol application, and at the end of pregnancy. Especially in S1 and S2 castration induces an increase of cellular autophagy. The nuclei become smaller; endoplasmic reticulum (ER), ribosomes, and Golgi apparatus are reduced; catabolism predominates. In S1 more giant lysosomes occur; the total number of lysosomes increases whereas acid phosphatase activity decreases at the same time. Sex differences which exist in untreated animals disappear. Substitution with estradiol causes an activation of the proximal tubule cells: Heterophagy predominates, and cellular autophagy is reduced. Nuclear size is unchanged; ER, ribosomes and Golgi apparatus show a clear increase. Giant lysosomes are absent in S1. On the whole lysosomes are larger, but less numerous than after castration. Acid phosphatase is highly active. All changes are most evident in S3. At the end of pregnancy the proximal tubule cells are "stressed" considerably: Pinocytotic activity increases, and large numbers of cell organelles and many lipid vacuoles can be observed. The basal lamina in S1 and S2 becomes thicker. Lysosomes enlarge and increase in number in all segments; giant lysosomes are absent in S1; acid phosphatase is extremely high. The results indicate that sex hormones directly influence the regulation of the proximal tubule cell; moreover, they are indirectly important for the functioning of the kidney via changes in the whole organism.