A significant but low-level association (relative odds, 2.0; P less than 0.05) was observed between the occurrence of breast cancer and the use of rauwolfia derivatives for 5 or more years in the study of 481 breast cancer cases and 1,268 controls from a joint national mammography screening project of the National Cancer Institute and the American Cancer Society. This association was confined to women over age 50 years who were also heavier than average. No confounding effects could be held responsible for this association after adjustment was made for variables such as presence of hypertension, weight, age at first pregnancy, and other breast cancer risk factors. Other antihypertensive and diuretic drugs as well as multiple drug use also exhibited some suggestive associations with breast cancer. Another group of 421 women with benign lesions at breast biopsy were also compared to the 1,268 controls. They showed a significant association between benign lesions and use of thiazides for 5 or more years (relative odds, 2.4; P less than 0.001) whether employed to treat edema or hypertension. Other antihypertensive and diuretic agents also seemed to show this association, but most of them were being used together with thiazides.