Background: Vitiligo is a hypopigmentation disease in which disorder in melanocytes causes the appearance of white patches in the skin. Endothelin-1 (ET-1) stimulates a variety of physiologic responses in melanocytes including increase in dendricity, mitogenesis, chemotaxis, pigment production in addition to activation of tyrosinase enzyme. Endothelin-1 increases the intracellular calcium concentration through endothelin beta receptor (ET-BR) in skin melanocytes. Aim of work: The aims of work were to detect gene expression of ET-1 and ET-BR in lesional and perilesional epidermis in a sample of vitiligo patients, to find a relation between gene expression of these markers and development of vitiligo, also to detect possible hidden susceptibility in perilesional skin of vitiligo patients through comparison with gene expression in skin of normal individuals & finally to use these genes expression data for the purpose of adding new strategies to the management of vitiligo. Patients and methods: Fifteen patients with vitiligo, from the outpatient clinic of Kasr AlAiny Hospital and National Research Center were involved in this study in which they were diagnosed clinically. A written consent was assigned by each patient before participation in the study. Every patient was subjected to the following: full history taking into consideration family history of vitiligo, exposure to stress, full general and dermatological examination (including VASI “vitiligo ). Conclusion: The ET axis may have a positive role in vitiligo. However one may suggest that this role is most probably through the down regulation of the expression of the ET-BR rather than a defect in the level of ET-1.