Natural killer (NK) cells have become a recent focus of interest in alopecia areata (AA) research. To further investigate their role in an established mouse model of AA, lesional skin from older C3H/HeJ mice with AA was grafted to young C3H/HeJ female mice, and NK cells were depleted by continuous administration of rabbit anti-asialo GM1. As expected, this significantly reduced the number of pure NK cells in murine skin, as assessed by NKp46 quantitative immunohistochemistry. Quite unexpectedly, however, the onset of hair loss in C3H/HeJ mice was accelerated, rather than retarded. NK cell depletion was accompanied by a significant increase in the number of perifollicular CD49b+T cells in the alopecic skin of anti-asialo GM1-treated mice. These findings underscore the need to carefully distinguish in future AA research between pure NK cells and defined subsets of CD49b+ lymphocytes, as they may exert diametrically opposed functions in hair follicle immunology and immunopathology. © 2010 John Wiley & Sons A/S.