AbstractUsing proposed Environmental Protection Agency histologic guidelines for selection of maximum tolerated doses in rodent carcinogenesis bioassays, our pathologists encountered a general problem with assessing the onset of hyperkeratosis and crusting from hematoxylin and eosin (H&E) preparations. Although the H&E stain is commonly used for routine analysis of skin samples for histopathology evaluation, it is usually limited in its capability to distinguish key lesions that are important in dermal bioassays. In seeking to identify a stain to act as an adjunct to the standard H&E method, we screened a series of stains. The best differentiation of early hyperkeratosis and crusting was seen with a modified fourcolor histochemical procedure. This procedure stains keratin a bright yellow and crusting exudates a bright pink to provide an early indicator of skin lesions. This stain is a possible adjunct to the standard H&E in diagnosis of rodent dermal bioassays. (The J Histotechnol17:33, 1994)