Background: The upregulation of HO-1 expression is required to protect melanocytes from apoptosis in response to UVA. Aim: We aimed to investigate the expression of the HO-1and HO-2 in vitiligo patients before and after treatment with PUVA. Patients: five groups involved in this study, group I: twenty vitiligo patients group II: ten vitiligo patients before starting treatment with PUVA, group III: ten healthy volunteers, group IV: ten vitiligo patients, group V: ten neonatal foreskin Methods: Biopsies were taken from lesional skin in group I before PUVA therapy and from repigmented skin, and from non lesional skin in groups II, IV and from normal skin in groups III,V. HO-1 mRNA was evaluated by RT-PCR technique. Immunostained cryosections and confocal microscopy were studied for HO-1 and HO-2 localization by melanocytes. Western blot was used to detect HO-1 and HO-2 protein expression in non lesional vitiligo melnaocytes and control melanocytes foreskin. Results: HO-1 mRNA is induced in repigmented vitiligo skin after PUVA treatment. Immunostained cryosections revealed elevation of HO-1 but not HO-2 expression after UVA. Detectable HO-1 protein expression by immunostaining was observed in repigmenting vitiligo skin following PUVA treatment with no change in level of HO-2. Western blot results showed upregulation of HO-1 and not HO-2 in non lesional vitiligo skin after UVA compared to control normal melanocytes which showed lower level of HO-1 upregulation. Conclusion: Adequate upregulation of HO-1 expression by melanocytes may be required for UV treatment responsiveness in vitiligo.