The authors measured serum concentrations by single and multiple sampling techniques in 347 women before, during, and after treatment with either hormonal or barrier methods of contraception. The prolactin responses to an intramuscular injection of estrogen also were evaluated in control and selected study patients. The incidence of hyperprolactinemia in oral contraceptive users was higher than control subjects (12 versus 5%). Hyperprolactinemia was best assessed by multiple blood sampling, it is often transient and resolves spontaneously in about 50% of women. The estrogen provocation study suggests that some women who develop hyperprolactinemia while taking oral contraceptives are more sensitive to the effects of exogenous estrogen and may be at greater risk of developing pill-related menstrual aberrations and hyperprolactinemia.