Introduction and background: PUVA therapy has long been considered a standard line of treatment for vitiligo that can stimulate melanogenesis. The response to PUVA therapy has always been deficient in some anatomical sites including hands, feet and periorificial areas. Treatment of these areas has always been a therapeutic challenge. Aim of work: To clarify causes of resistance at those sites, by studying the expression of stem cell factor on keratinocytes and c-kit receptor on melanocytes in both resistant and responding lesions of vitiligo before and after photochemotherapy. Patients and methods: The study included twenty patients of generalized active vitiligo. Four skin biopsies: 2 biopsies (1 lesional and 1perilesional) from areas expected to respond and 2 biopsies (1 lesional and 1perilesional) from areas expected to resist were taken from each patient before PUVA and as soon as repigmentation starts other four skin biopsies were taken in the same pattern. Immunohistochemical staining was done for each section by Heamatoxylin & Eosin, Melan-A, stem cell factor, c-kit protein. Results: Before PUVA therapy, there was increased expression of SCF and absence of c-kit from lesional skin in both groups. Areas resistant to treatment showed significantly lower hair follicle density, epidermal melanocyte density by Melan-A staining, lesional SCF expression as well as perilesional c-kit expression. After PUVA therapy there was a significant decrease in SCF expression in both groups but significant rise in c-kit expression was noted only in responding lesions. Conclusion: Areas resistant to treatment in vitiligo show lower numbers of hair follicles, melanocytes and lower expression of SCF as well as c-kit compared to responding areas. These differences could be behind the resistance to PUVA therapy. A defect in SCF/c-kit system interaction that fails to be corrected by PUVA could be suggested.