Viscum album L. (mistletoe) extracts are widely used in adjuvant cancer therapy. In contrast to purified components, such as mistletoe lectins and viscotoxins, whole plant extracts of mistletoe resulted in DNA stabilizations in cyclophosphamide-treated lymphocytes but also provided cytotoxicity in tumour cells and lymphocytes. The killing capacities of mistletoe extracts were host tree-specific and not correlated with mistletoe lectin or viscotoxin content. In human lymphocytes, only mistletoe lectins induced a pathway of apoptotic killing. Within 72 h, the lectin B chains also increased the number of lymphocytes undergoing apoptosis. This finding suggests that inhibition of protein synthesis by the A chain of the hololectin may accelerate a receptor-mediated killing pathway induced by the B chains. An unexpected finding was related to the mistletoe-mediated killing, which was more effective against CD8+T cells with an activated phenotype than CD19+ B cells and CD4+ T cells. In vitro treatment of human neutrophils with mistletoe resulted in a slight decrease of phagocytosis and burst activity. The observed dose-dependent occurrence of two neutrophil subsets with different burst activities indicates differences in their susceptibility to mistletoe and suggests the implication of an induction of the apoptotic killing pathway.