Background The mechanisms involved in laser-mediated hair removal remain unclear. One means of reducing hair growth is alteration of follicular stem cells. Objective We sought to examine the effects of laser hair removal on the immunohistochemical staining properties of human hair follicles, including the putative stem cells of the bulge region. Methods Treatment of unwanted axillary hair was performed on one side using an 800 nm–wavelength diode laser and on the other side using a 1064 nm–wavelength neodymium:yttrium-aluminum-garnet laser. Serial skin samples were obtained at baseline and various times after treatment and stained using immunohistochemical techniques. Results Hair shafts were thermally altered, but the immunostaining properties of much of the follicle, including the bulge region, remained generally unchanged. Limitations This study only addressed the acute immunohistochemical changes found after a single treatment using specific laser parameters. Conclusions Laser-mediated hair removal does not appear to work by frank destruction of follicular stem cells. Other mechanisms including functional alteration of these cells may underlie the clinical efficacy of the procedure.