Pathogenic mechanisms involved in the blister formation of epidermolysis bullosa (EB) are not clearly understood at present. In this paper, we attempted to produce experimental blistering in vitro similar to the histologic picture of EB simplex (EBS) and recessive dystrophic EB (RDEB). It was demonstrated by light and electron microscopy that the medium containing fresh blister fluids from the patients with EBS or RDEB could produce similar histologic features in normal human skin (in vitro) to those of the skin lesions of patients (in vivo). This observation may open new avenues of approach to studying these diseases.