Side effects of cytostatic treatment include development of anemia resulting from either decreased generation or accelerated clearance of circulating erythrocytes. The present study explored whether treatment with paclitaxel (Taxol®) triggers erythrocyte programmed cell death. Blood was drawn from cancer patients before and after infusion of Taxol®. The treatment significantly decreased the hematocrit and significantly increased the percentage of annexin-V-binding erythrocytes in vivo. In vitro incubation of human erythro-cytes with paclitaxel again significantly increased annexin-V-binding and augmented the increase of annexin-V-binding following cellular stress. The enhanced phosphatidylserine expo-sure was not dependent on caspase-activity but paralleled by erythrocyte shrinkage, increase of cytosolic Ca2+ activity, ceramide formation and activation of m-calpain. Externalization of phos-phatidylserine was similarly induced by docetaxel but not by carbo-platin or doxorubicin. In conclusion, our data suggest that paclitaxel-induced anemia is partially due to induction of erythro-cyte programmed cell death by this common anti-cancer drug.