Administration of tamoxifen (an antiestrogen) produced an 80% parasite load reduction in female mice, and a weaker effect of 50% in male mice. This protective effect was associated in both sexes, with an increase in the mRNA levels of interleukin (IL)-2 (a cytokine associated with protection against cysticerci) and IL-4 (no effect on infection). tamoxifen treatment modified 17-β estradiol production in females, whereas serum testosterone was not affected. However, the expression of the 2 types of estrogen receptor (ER), i.e., ER-α and ER-β, in the spleen of infected mice of both sexes, was decreased by tamoxifen treatment. In vitro, treatment of Taenia crassiceps with tamoxifen reduced reproduction and loss of motility. These results indicate that tamoxifen treatment is a new therapeutic possibility to treat cysticercosis, because it can act at both ends of the host–parasite relationship, i.e., by increasing the cellular immune response protective against the parasite and by directly affecting the parasite's reproduction and survival.