Twenty-three seasonally anovulatory mares, housed at two separate farms, were treated with 50 mg of estradiol cypionate (ECP) and 3 g of sulpiride in January to study factors that contributed to success of the treatment (response = ovulation within 28 days). Every other day, blood samples and pretreatment secretagogue challenges were used to characterize prolactin, luteinizing hormone (LH), insulin-like growth factor-I, leptin, and insulin concentrations. Ovaries of each mare were scanned via ultrasound regularly until detection of a 32–35 mm follicle, at which time the mare was artificially inseminated. Prolactin was stimulated in all treated mares and was similar (P > .05) in responding and nonresponding mares. Nine mares, all at the same farm (Ben Hur; farm effect, P = .006), responded with preovulatory sized follicles within 20 days of treatment. Five of the 9 were inseminated and 3 conceived. Retrospective analysis revealed that of the mares responding, body condition score (P = .03), body weight (P = .02), plasma concentrations of insulin (P = .01) and leptin (P = .09), and pretreatment response of LH to gonadotropin-releasing hormone (P = .106) were higher in responding than in nonresponding mares. In general, factors that differed and may contribute to whether a given mare responds to this ECP-sulpiride protocol were mainly characteristics pointing toward well-nourished mares. Minor nutritional differences between farms likely played a role in the lack of success on the one farm. Also, the LH response to gonadotropin-releasing hormone prior to treatment may be indicative of the subsequent LH response to ECP-sulpiride and hence the ovarian response.