The effects of androgen deprivation and estrogen stimulation on rat coagulating gland were determined by immunohistochemistry and morphometric quantification of different tissue compartments. In castrated or estrogen-treated or estrogen-treated castrated animals, the reduction of the glandular lumen is the most obvious morphological alteration, which is accompanied by an increase in stromal tissue, especially within the lamina propria. Regressive changes occur most rapidly in castrated animals (already by the end of the first week), slower in estrogen-treated castrated animals, and still slower in estrogen-treated normal animals. In castrated animals, epithelium shows a reduction of rough endoplasmic reticulum, loss of secretory blebs, and a decrease of cell size and immunoreactivity for secretory transglutaminase. The reduction of glandular lumen results from an impressive increase in connective tissue of the lamina propria. Smooth muscle cells become atrophic in castrated animals, less so in estrogen-treated animals and in castrated estrogen-treated animals. A relative increase in thickness of the smooth muscle cell layer occurs in all experimental groups and is most obvious in estrogen-treated normal animals. The proportion of myofilament and intermediate filament proteins (smooth muscle-specific actin and desmin immunoreactivities) remains nearly unaltered in these cells after hormonal challenge. A redistribution of intermediate filaments occurs forming thicker bundles within the cells. No indication for increased mitotic activity of estrogenized smooth muscle cells has been found. After castration, and after estrogen treatment, the fibroblasts and the smooth muscle cells, respectively, appear responsible for the architectural changes within the coagulating gland. Reactions of the stroma are differentially regulated after estrogen treatment and androgen deprivation. No indication for increased biosynthetic activities of smooth muscle cells has been observed in any of the experimental conditions. © 1993 Wiley-Liss, Inc.