Treatment of hyperprolactinemia with oral bromocriptine has been associated with a high incidence of side effects. The authors recently demonstrated that, in normal women, the vaginal route of administration was an effective and safe alternative to oral bromocriptine. To evaluate the effectiveness of vaginal bromocriptine in treating women with hyperprolactinemia, the authors treated 15 hyperprolactinemic women with daily vaginal administration of 2.5 mg tablets of bromocriptine. Serum prolactin (PRL) levels and vital signs were measured daily for 6 days, then weekly for 4 weeks. Gastrointestinal side effects were limited to a single episode of mild nausea, and two cases of transient constipation. In all patients there was a dramatic initial reduction in PRL in response to a single 2.5 mg dose of bromocriptine. In 13 patients PRL levels were maintained within the normal range with daily administration of 2.5 mg, whereas in two patients, PRL levels remained higher than normal despite an increase in bromocriptine dose to 5 mg. These results suggest that short term use of vaginal bromocriptine is a safe and effective method of therapy for hyperprolactinemia.