The increasing use of normal donors for leukapheresis to provide granulocyte concentrates requires careful monitoring of recruitment and operational procedures to minimize donor health risks. Of 18,288 leuka- and leukaplateletphereses performed in American Red Cross regional blood services during a 12-month period, only 0.27% were discontinued because of acute donor reactions. None of these reactions had serious or long-term consequences for the donors. The potential toxicities of corticosteroids and hydroxyethyl starch, and the theoretical hazards of lymphocyte depletion, raise unanswerable questions concerning long-term safety, although no serious adverse reactions related to these factors have been observed. Critical factors for leukapheresis donor safety are: selective donor recruitment, adherence to operational protocols, and continuous and informed interest of physicians responsible for pheresis programs. Additional data are needed to assess the effects of repeated leukapheresis on donors and to establish rational guidelines for donor recruitment.