The bacterially fermented mistletoe preparation Iscador, used in cancer therapy for 30 years, and the recently prepared unfermented preparation, have been tested on rat hepatoma tissue culture (HTC) cells and human leukemia Molt 4 cells. As observed by phase-contrast microscopy, treatment of HTC cells with fermented or unfermented Iscador, at a concentration corresponding to 1 mg of fresh plant per milliliter culture, led to rapid lysis of cellular membranes. At a lower concentration, 0.1 mg/ml, unfermented Iscador led to the formation of polynucleated cells. On Molt 4 cells, fermented Iscador also produced cytolysis but after a longer time of action. Unfermented Iscador showed a much stronger cytotoxic effect on these cells than on HTC cells. Fermented Iscador was slightly more potent than unfermented Iscador in inhibiting the growth of HTC cells, but on Molt 4 cells fermented Iscador was less active than unfermented Iscador. DNA synthesis, measured by [3H]thymidine incorporation in HTC and Molt 4 cells, was inhibited by fermented and unfermented Iscador with the same type of differences of action as on cell growth. Fermented Iscador contained a low amount of lectins, approximately 100 ng/ml, while unfermented Iscador contained about 10 times more. A purified mistletoe lectin produced effects on HTC and Molt 4 cells similar to those of unfermented preparations. HTC cells were 100 times less sensitive to this lectin than Molt 4 cells. These results are discussed in relation to the known biological effects of lectins.