Although it is widely believed that non-segmental vitiligo (NSV) results from the autoimmune destruction of melanocytes, a clear understanding of defects in immune tolerance that mediate this uncontrolled self-reactivity is still lacking. In the present study, we systemically evaluated circulating regulatory T (Treg) cells, including CD4(+) CD25(+) FoxP3(+) Treg cells and invariant natural killer T (iNKT) cells, as well as naïve and memory CD4(+) and CD8(+) T cells and their cytokine production, in a cohort of 43 progressive NSV patients with race-, gender- and age-matched healthy controls. We found that the general immunophenotypes of CD4(+) and CD8(+) T cells and percentage of CD4(+) CD25(+) FoxP3(+) Tregs are comparable between NSV and healthy controls. However, percentage of peripheral iNKT cells were significantly decreased in NSV patients compared to that in healthy controls. Our data confirm the previous notion that the percentage of peripheral CD4(+) CD25(+) FoxP3(+) Tregs remains unaltered in NSV, and suggest the involvement of defective iNKT cells in the pathogenesis of NSV. Significance:  The present study represents, to our knowledge, the first large scale systemic analyses of peripheral T cell immunophenotypes, from conventional T cells to regulatory T cells (Tregs), in a large cohort of progressive NSV patients. Our results show that there are no significant differences on the basic immunophenotypes of conventional CD4/CD8 T cells and the percentages of CD4(+) CD25(+) FoxP3(+) Tregs between NSV patients and healthy controls. However, the percentages of peripheral invariant natural killer T (iNKT) cells, which have been thought to play a major role in autoimmune diseases, were significantly decreased in NSV patients. Thus, our results highly suggest that iNKT cells may be involved in the immnuopathogeneis of NSV. © 2012 John Wiley & Sons A/S