Background: Pemphigus vulgaris, the most common form of pemphigus, is due to the production of auto-antibodies directed against adhesion molecules (desmoglein 1 and 3) that belong to the cadherin family. B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) may play a significant role in autoimmune diseases such as pemphigus vulgaris. Only a few studies have been done on the level of APRIL and BAFF in PV patients but none have investigated both levels; therefore, determination of both proliferation inducing ligands (BAFF and APRIL) in pemphigus vulgaris is of significant importance and was considered as the goal of the present study. Methods: This analysis included 22 patients with PV and 22 sex and age matched healthy controls. None of the patients had previously been treated with corticosteroids or any immunosuppressive drugs in the previous three months. The BAFF and APRIL levels were evaluated in patient and control groups by use of ELISA method. Results: Comparison of the serum levels of BAFF and APRIL between patients and controls was done using Mann-Whitney U test. The BAFF levels in our 22 patients and control sera were undetectable. On the other hand, concentrations of APRIL in 22 cases were 2.09+/-4.94 and 0.85+/-2.01 in the control group. Conclusion: BAFF levels were undetectable in cases and the difference in APRIL levels between patient and control groups was not significant (p=0.28). So, it can be concluded that although BAFF and APRIL may play a role in autoimmune diseases, their role in pemphigus vulgaris is doubtable.