Background: On the basis of clinical and histopathologic similarities to human paraneoplastic pemphigus (PNP), we recently identified the first case of PNP in a nonhuman species, the dog. Objective: To determine a similar pathogenesis in both species, the present study aimed to define whether common antigens are targeted in dog and man. Methods: Canine and human PNP sera were used in parallel to immunoprecipitate ¹⁴C-labeled human keratinocyte antigens. The immunoreactive proteins were then identified by immunoprecipitation of canine keratinocyte extracts with specific antibodies to the antiplakin family members follwed by immunoblot analysis using canine and human PNP sera. Results: Protein bands of 210, 190, 170, and 130 kd were identified in dogs and humans. In both species, envoplakin and periplakin were demonstrated as antigens. Anti-desmoglein 3 antibodies could not be demonstrated in canine PNP, but in human PNP. Conclusion: These results demonstrate that canine PNP closely correlates to the human counterpart and may therefore represent an excellent model for the human disease.(J Am Acad Dermatol 1999;40:682-5.)