Hyperprolactinemia is associated with reproductive acyclicity in zoo African elephants (Loxodonta africana) and may contribute to the non–self-sustainability of the captive population in North America. It is a common cause of infertility in women and other mammals and can be treated with the dopamine agonist cabergoline. The objectives of this study were to assess prolactin responses to cabergoline treatment in hyperprolactinemic, acyclic African elephants and to determine the subsequent impact on ovarian cyclic activity. Five elephants, diagnosed as hyperprolactinemic (>11 ng/ml prolactin) and acyclic (maintenance of baseline progestagens for at least 1 yr), were treated with 1–2 mg cabergoline orally twice weekly for 16–82 wk. Cabergoline reduced (P < 0.05) serum prolactin concentrations during the treatment period compared to pretreatment levels in four of five elephants (11.5 ± 3.2 vs. 9.1 ± 3.4 ng/ml; 20.3 ± 16.7 vs. 7.9 ± 9.8 ng/ml; 26.4 ± 15.0 vs. 6.8 ± 1.5 ng/ml; 42.2 ± 22.6 vs. 18.6 ± 8.9 ng/ml). However, none of the females resumed ovarian cyclicity based on serum progestagen analyses up to 1 yr posttreatment. In addition, within 1 to 6 wk after cessation of oral cabergoline, serum prolactin concentrations returned to concentrations that were as high as or higher than before treatment (P < 0.05). One elephant that exhibited the highest pretreatment prolactin concentration (75.2 ± 10.5 ng/ml) did not respond to cabergoline and maintained elevated levels throughout the study. Thus, oral cabergoline administration reduced prolactin concentrations in elephants with hyperprolactinemia, but there was no resumption of ovarian cyclicity, and a significant prolactin rebound effect was observed. It is possible that higher doses or longer treatment intervals may be required for cabergoline treatment to result in permanent suppression of prolactin secretion and to mitigate associated ovarian cycle problems.