Euthymic hairless guinea pigs were compared to normal haired guinea pigs to determine whether the hairless guinea pig is a suitable animal model for studying sulfur mustard (HD) induced vesication of skin. Neat HD was applied to the skin for 30 minutes, and the exposed skin was examined at 24 and/or 48 hours post-exposure for gross, histopathologic, and/or ultrastructural lesions. The hairless guinea pig proved to be a superior animal model compared to the haired guinea pig because it was more sensitive to HD, the lesions were more readily scored, and the animal was much more convenient to use. Keywords: Guinea pigs; Hairless guinea pigs; Mustard; Vesicant.