Although reserpine has an important role in treating patients with hypertension, its appeal was sharply reduced a decade ago when an alleged relationship to breast cancer was reported in case-control studies. Since the relationship was not confirmed in subsequent research and analyses, the original association is now regarded as erroneous. Since patients with cardiovascular disease were rejected as possible controls in the original reserpine-breast cancer case-control study, we suspected that the false association may have been produced by a phenomenon called exclusion bias. This bias can arise in case-control studies if patients with a particularly high (or low) rate of prior exposure to the alleged etiologic agent are excluded from the selection of either cases or controls, but not from both. To test that suspicion, we recapitulated the original study, in another medical setting. The cases were 257 women with breast cancer; and the controls were 257 hospitalized women matched according to date of admission, age, and race. The overall data showed no association between reserpine and breast cancer (odds ratio [OR] = 1.1), but when we excluded 101 women with cardiovascular disease from the control group, the OR rose to 2.5. The results suggest that exclusion bias played an important role in creating the false association between reserpine and breast cancer.