Theoretically, the immunization of experimental animals with an anti-idiotype antibody may elicit antibodies that recognize epitopes like the original idiotype; this is archived via internal images. Using this strategy, we attempted to produce anti-epithelial antibodies in Balb/c mice immunized with a pemphigus anti-idiotypic determinant. First, when an anti-idiotype antibody was produced in rabbits by immunization with pemphigus immunoglobulin G (IgG), the anti-idiotypic activity was tested successfully. The anti-idiotype IgG was digested with pepsin and purified by gel filtration chromatography to obtain F(ab')(2) fragments, which were used to immunize Balb/c mice. A control group was immunized with normal IgG. The experimental animals immunized with anti-idiotype F(ab')(2) fragments developed anti-epithelial antibodies in the following two months. The elicited antibodies had anti-desmoglein 1 specificity. Additionally, the skin biopsies of these animals exhibited antibody deposition along intercellular spaces of epidermis, and 25% of them developed blisters. Sera and skin biopsies of control Balb/c mice group were negative. In conclusion, the immunization with pemphigus anti-idiotype antibody may elicit anti-epithelial antibodies via internal images. This experimental approach can be used to understand the pathogenic mechanisms of pemphigus.