Objective: To evaluate the possible role of herpes simplex virus type I (HSV-I) infection and apoptosis in the etio-pathogenesis of pemphigus vulgaris (PV). Patients & Methods: This study included 29 patients with PV arid 7 apparently healthy subjects as controls. Patients' -were grouped into 3 groups: I) Recent acute onset (6 cases); (II) Chronic exacerbated under steroid therapy (16cases) & (III) chronic controlled with steroid therapy (7cases). Apoptosis was detected in peripheral blood monocytes (PBMC) using Flow-cytometry and that in the skin by TUNEL. HSV-I DNA was detected in PBMC and the skin using PCR. The antibody titer of serum IgG for HSV-I was detected using indirect immuno-fluorescence technique (IF). Results: The apoptotic indices in both PBMC and skin were significantly higher in PV, especially with exacerbation (group II) with- mean: values (38.36±14,97) & (I9.74±2.04) compared to controls (5.1±2.81) & (0.93±0,03). Apoptosis was detected in acantholytic and/or nearby skin. There was significant increase in apoptotic indices in PBMC and skin in association with presence of HSV-I DNA in PBMC especially for group II followed by group-I. Significant increase of these indices was also, found with positive HSV-I in the skin (P