The sensitivity of hairless mice to cutaneous chemical carcinogenesis has been compared with that of normal mice of the same strain with hair. A single application of 125 µg methylcholanthrene in benzene was given to 48 hairless male mice (hr/hr Oslo strain) and to 96 male mice of the same strain with hair. Among hairless mice there were 94% papilloma-bearing animals with a total of 5.9 tumors per animal after 18 months of observation, compared to 22% papilloma-bearing animals with an average of 0.3 tumors per animal among the mice with hair. The hairless mice included 31% carcinoma-bearing and 23% sarcoma-bearing animals, whereas only 1 % of the mice with hair were carcinoma bearing and 3% were sarcoma bearing. Hairless mice of the hr/hr Oslo strain are thus not refractory to chemical carcinogenesis, but under the experimental conditions used in this study they are significantly more sensitive than are mice from the same strain with hair. Giovanella et al. reported almost opposite results in 1970 and came to the general conclusion that hairless mice are refractory to chemical carcinogenesis due to lack of hair follicles. Since hairless mice always have some hair follicles and rudimentary pilosebaceous appendages, comparisons between chemical carcinogenesis in hairless mice and mice with hair can neither strengthen nor weaken any theory about the hair follicle origin of epidermoid carcinomas of mouse skin.