We evaluated the effectiveness of 2 dopamine antagonists as treatments for fescue toxicosis in horses. Sixteen gravid mares were assigned by breed and expected foaling date to 1 of 3 treatment groups: endophyte-infested control; 1.1 mg of domperidone/kg of body weight/d; and 3.3 mg of sulpiride/kg/d. Mares were pastured on endophyte-infected fescue and received 0.454 kg of a corn and dried molasses carrier containing the drug treatment. Treatment started 30 days prior to expected foaling date and continued until parturition. Blood samples were collected, and mammary gland scores were recorded every 5 days. Body weight and body condition scores were obtained every 28 days. Serum was analyzed for prolactin, progesterone, and estradiol-17 beta concentrations. Domperidone-treated mares had shorter (P = 0.09) gestation duration and foaled closer (P = 0.07) to their expected parturition date than did control mares. Mammary gland scores were higher (P < 0.05) for domperidone-treated mares than for control mares. By 4 and 9 days after the start of treatment, serum prolactin concentration was higher (P < 0.05) in domperidone-treated mares and sulpiride-treated mares, respectively, than in control mares. Domperidone- and sulpiride-treated mares had higher (P < 0.05) serum progesterone and lower (P < 0.01) estradiol-17 beta concentrations than did control mares. These results indicate that domperidone may offer considerable potential as a treatment for fescue toxicosis in horses.