Background: Rituximab is an effective treatment for inducing remission in pemphigus vulgaris (PV) refractory to conventional immunosuppression. Re-treatment is required on relapse, but there are currently no reliable biomarkers in predicting clinical relapse. Method: We prospectively followed 18 PV patients previously treated with rituximab at Westmead Hospital over a 2-year period. Disease activity was assessed by pemphigus disease activity index (PDAI) along with desmoglein (dsg), intercellular cement substance (ICSA) antibody titres, total B-cell and memory B-cell (CD19+CD27+) counts. Results: 9/18 patients relapsed requiring further rituximab administration. Of these, relapse was preceded by dsg elevation in 5/9 and B-cell return in 2/9 patients. Chronic elevation in dsg antibodies and B-cells were seen in the remaining 2/9 patients with no relationship to PDAI. Of the 9 patients in clinical remission, 5 had normal dsg antibody levels. Review of their clinical data prior to the study suggests correlation of dsg titre elevation with disease relapse. The remaining 4 patients had chronic elevation of dsg antibodies and B-cells. There was no additional information gained from measuring memory B-cells and no correlation between PDAI and ICSA antibody levels. Discussion: Both dsg antibody levels and B-cell counts can predict relapse in subgroups of rituximab-treated refractory PV patients.