An epidemiologic study was carried out in 2106 women 46-63 years of age to determine risk factors associated with their compliance or noncompliance with estrogen replacement therapy (ERT). Data were obtained from prescription refill and medical claims information from centralized prescription and medical claims databases of a United Healthcare-affiliated health plan in Minnesota. Study participants filled their first ERT prescription during calendar year 1989 or 1990. Our results indicate that women who are older, use a progestin, experience hormone replacement therapy side effects, or see a gynecologist or male physician are more likely to be noncompliant. Women who have cardiovascular problems, experience menopausal symptoms, or use transdermal estrogen are more likely to be compliant. These results suggest that the factors associated with compliance are those that indicate that women perceive a benefit from ERT use. The factors associated with noncompliance are hormone side effects and gender and specialty of the physician prescribing the estrogen.