Tamoxifen (TAM), which binds to estrogen receptors and can act as an estrogen antagonist, was incorporated into the diets of swine and mink to determine if it would ameliorate the effects of the estrogenic mycotoxin zearalenone (ZEN). Sows and female mink were fed diets containing 2 ppm (swine) or 20 ppm (mink) ZEN and/or 10 ppm TAM from day 30 of gestation through weaning (swine) or from 2 months prior to breeding through weaning (mink). The diets containing ZEN and/or TAM did not adversely affect reproduction in the sows. Although some hyperestrogenic effects on testes, uterine and ovarian weights were observed in the F1 piglets at 21 days of age, subsequent breeding performance was not affected. All the female mink exposed to ZEN mated, but only 25% whelped. No mink fed TAM (singly or in combination with ZEN) mated. Necropsy of these unmated females fed TAM revealed consistent severe pyometra. Histological examination of the reproductive tracts of the ZEN, TAM and ZEN + TAM-treated mink showed similar alterations, including ovarian follicular atrophy and degeneration, and mild to severe uterine atrophy, pyometra and endometritis. The results of these studies indicate that TAM was not effective in ameliorating the hyperestrogenic effects of ZEN in swine and mink, but rather it acted as an estrogen agonist.