Pemphigus vulgaris (PV) is an autoimmune mucocutaneous blistering disease. Recently, patients with mucosal involvement have been described to have autoantibodies to desmoglein 3 (dsg), while patients with mucocutaneous disease have autoantibodies to dsg 1 and dsg 3. The objective of this study was to prospectively analyze, over a 24-month period, the influence of intravenous immunoglobulin (i.v.Ig) therapy on autoantibody titers to dsg 3 and dsg 1, in two groups of patients with severe PV. Group A consisted of 11 patients with mucocutaneous involvement and group B consisted of 10 patients with only mucosal involvement. Levels of autoantibodies to dsg 3 and 1 were measured by ELISA, at monthly intervals. Prior to therapy initiation, group A patients' sera showed a high ELISA index value of both dsg 3 and 1 antibodies, while group B patients had a high index value to only dsg 3. During i.v.Ig therapy, a progressive decline in the ELISA index values was observed in all patients. After the initiation of i.v.Ig therapy, in group A, a statistically significant reduction (p < 0.05) in ELISA index value to dsg 3 and 1 was detected after four and five months, respectively. In Group B, a significant decline in the mean autoantibody titer values to dsg 3 (p < 0.05) was observed after six months of i.v.Ig therapy. Group A patients had a negative ELISA index value to dsg 3 and 1 after a mean period of 21 and 20 months, respectively. Group B patients had a negative dsg 3 score after a mean period of 22 months. These results indicate that autoantibody titers to dsg 3 and 1, as measured by ELISA, can be used to monitor the serological response to treatment in PV patients. A sustained serological remission is observed in patients treated with i.v.Ig therapy. .