Based on three test methods (inhibition of cell multiplication in vitro, effect on fibroblast cultures, and tumor inhibition in animals) it is shown that in some cases minor chemical modifications of the structure of podophyllum compounds cause drastic changes in activity, quantitatively as well as qualitatively. The compounds discussed more specifically are: podophyllotoxin, its 4'–demethyl derivative, epipodophyllotoxin, 4'–demethyl–epipodophyllotoxin as well as glucosides and benzylidene–glucosides of these four compounds, and in addition, 4'–demethyl–epipodophyllotoxin ethylidine glucoside (VP 16–213).