OBJECTIVE: To determine whether long-term postmenopausal estrogen therapy is associated with use of other prescription medications. METHODS: Using computer pharmacy records from 1969 to 1973 for members of the Kaiser Permanente Medical Care Program in San Francisco, we identified the 215 most commonly used prescription medications in the pharmacy database and recorded their use by 232 postmenopausal long-term estrogen users and by 222 postmenopausal age-matched nonusers. These medications were grouped into 39 therapeutic classes. Classes of medications used by estrogen users and nonusers were compared. RESULTS: A statistically significant difference in use was seen for 21 of the 39 medication classes; of these 21 classes, 20 (95%) were used more frequently and 1 less frequently by estrogen users. Differences between estrogen users and nonusers were greatest for thyroid hormone preparations (estrogen user/nonuser multivariate odds ratio = 25.6, 95% confidence interval 5.9-112) and antimigraine preparations (11 recipients among estrogen users, none among nonusers). Postmenopausal women using estrogen were more likely than nonusers to use additional medications. CONCLUSION: Greater use of certain prescription medications by estrogen users than by nonusers should be considered in studying the health effects of estrogen replacement therapy.