A case-control study was conducted to determine whether use of oral contraceptives (OCs) is associated with an increased risk of prolactin-secreting pituitary adenomas. Two hundred twelve women with such adenomas (140 of which were surgically confirmed) were recruited from four clinical centers and interviewed and matched by age and race to neighborhood control subjects. In addition, 119 hyperprolactinemic patients with amenorrhea and/or galactorrhea (A/G) who had normal or equivocal tomograms and 205 normoprolactinemic women with A/G were also interviewed and matched to neighborhood control subjects. No increase in relative odds (RO) for any of these groups of patients was found for use of OCs (pituitary adenoma cases versus controls RO = 1.33, 95% confidence intervals [CI] = 0.81 to 2.22; equivocal cases versus controls RO = 1.35, 95% CI = 0.69 to 2.70; secondary A/G cases versus controls RO = 0.67, 95% CI = 0.37 to 1.18). History of infertility (RO = 25.5, 95% CI = 8.49 to 76.6), of menstrual problems or A/G (RO = 4.47, 95% CI = 2.21 to 9.05), and of nulliparity (RO = 4.36, 95% CI = 2.10 to 9.04) were each associated with a significantly increased risk of pituitary adenomas. The results of this study do not indicate any increase in risk of pituitary adenomas as a result of using OCs.