The estrogen receptor-α (ERα) knockout mouse (αERKO) lacks ERα throughout development; therefore, an adult model for the study of estrogen effects in male mice was recently developed using the antiestrogen ICI 182,780. However, differences between species have been noted during immunostaining for ERα in the male tract as well as in response to treatments with antiestrogens. Therefore, we developed the antiestrogen model in the adult male rat to test, in another species, the hypothesis that estrogen regulates fluid reabsorption in efferent ductules. Estrogen receptor in the rat was blocked using ICI 182,780 for 100–150 days. Male Sprague-Dawley rats were treated weekly with s.c. injections of ICI 182,780 (10 mg) or castor oil (as control). The effects of ICI included testicular atrophy and infertility, similar to terminal effects in the αERKO male. Additionally, ICI induced dilations of the rete testis and efferent ductules and a reduction in the height of the ductule epithelium, which are changes similar to those in both αERKO and ICI-treated mice. One difference between species was a large variation in effects on the rat efferent ductule epithelium, including a transient increase in the number of periodic acid-Schiff-positive, lysosomal-like granules. These data confirm that estrogen is required for normal function of the efferent ductules and is essential for long-term fertility in the male rodent.