The possibility that sex steroids act to promote the association of lysosomes with nuclei was studied by 2 methods in the secretory epithelium of ventral prostate of castrated rats treated with androgens: (a) electron microscopic (EM) examination of intact tissue and (b) study of fresh nuclear suspensions isolated from prostate homogenates using the fluorescing dye acridine orange (AO) and EM. AO-stained particles in nuclear suspensions were found to correspond to either (i) section granules, (ii) primary lysosomes or (iii) heterogenous dense bodies (HDB), considered to be lysosomes. Intact prostate tissue and crude nuclear suspensions were studied in adult rats 3-21 days after castration and in normal rats. Changes in nuclear architecture are evident 8 days or more after castration; the number of HDB increase while secretion granules and primary lysosomes decrease. Whether from prostate of castrated, normal or hormone-treated animals, a small number of the lysosomal HDB or primary lysosomes are seen closely apposed to epithelial cell nuclei. In response to short-term testosterone administration (15 or 60 min) in 10- and 21-day castrate rats, chromatin distribution appears to become more condensed; yet the number of associations of nuclei with lysosomal elements does not change. These studies of androgen action in rat ventral prostate (a classical target organ for the study of androgen action) provide no evidence to support the idea that lysosomal association with, or invasion of, nuclei in target cells is a general feature of sex steroid hormone action.