The four lignans: podophyllotoxin, 4'-demethyl-podophyllotoxin, alpha-peltatin and beta-peltatin represent the podophyllin ingredients believed to exert lesional necrosis after application to condylomata acuminata. This study comparatively evaluates cutaneous cytodestructive potency of these drugs, as evaluated by measurement of epidermal and dermal 3H-thymidine incorporation and injury of dermal microcirculation at intervals in the range of 9--168 h after application to hairless mouse skin. Influence on DNA-synthesis was measured using a disc technique for isolation of standardized skin areas followed by alkali extraction of DNA from respective tissues after separation through potassium bromide incubation. Any capillary injury was demonstrated by visual assessment of leakage of i.v. injected trypan blue to test areas. An analytical method compensating for variations in DNA synthesis in individual controls is presented. Using 0.5% preparations of the lignans, podophyllotoxin most consistently influenced the variables indicating cytodestructive effect, while 4'-demethyl-podophyllotoxin exerted the weakest degree of damage.