Whole blood donation is recognized to be extremely safe, yet there have been reports of serious problems stemming from whole blood donation, and so-called "donor reactions" are regularly seen. While the physiologic causes of the common donor reactions are not completely understood, some effects of whole blood donation (such as transient iron deficiency) are understood but probably not significant. In order to avoid accepting any volunteer donor who might be at risk of a serious reaction, we may have been overly cautious in exclusion of potential donors. The pheresis donor is subjected to potential depletion of the protein or cellular elements being removed, problems caused by the device used for automated pheresis, or problems related to the infusion of potentially toxic substances. Documented benefit to the patient must balance these additional risks.