Chemical carcinogenesis of human skin was investigated using human skin xenografts (16 full thickness and 48 split thickness skin grafts) transplanted to CB-17-scid (SCID) mice. Topical application of a carcinogen, i.e. 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene, methylcholanthrene or N-methyl-N'-nitro-N-nitrosoguanidine, to the human skin xenografts once a week for 25-30 weeks failed to produce skin tumors. Both DMBA application plus UV-B irradiation and alternate applications of the above four carcinogens in combination with UV-B irradiation also failed to produce tumors. All of these treatments induced skin papillomas in skins of host SCID mice. DMBA induced skin papillomas in allogenic CD-1 mouse skin grafts transplanted to SCID mice. These results indicate that susceptibility of human skin to these carcinogenic stimuli is much lower than that of mouse skin.