The fur of the C57BL/vi.vi mouse is black at 6 weeks of age. By 6 months of age the animals are white and there are no identifiable pigment cells within the epidermis or hair bulbs. Human subjects with vitiligo exhibit loss of epidermal pigment cells. The loss of pigment cells in human subjects with vitiligo has been associated with loss of cutaneous immune reactivity to contact allergens. Therefore, studies were performed to determine whether loss of pigment cells in these depigmenting mice also was associated with loss of the cutaneous immune response. The number of Ia-positive (Ia +) Langerhans cells (LC)/mm2 on the back and the ear, the sites of sensitization and challenge with dinitrofluorobenzene (DNFB), was quantified before, during, and after depigmentation. We observed that there were fewer LC/mm2 on the back and the ear before and after pigment loss in the graying mice than in the normal control C57BL/6 mice. The young pigmented C57BL/vi.vi mice were capable of developing moderate contact hypersensitivity; the older depigmented mice did not sensitize to DNFB. We conclude that the depigmented mice, like human subjects with vitiligo, have a loss of contact hypersensitivity associated with a loss of pigment cells within the epidermis. In the mouse, loss of melanocytes is associated with a decrease in the population density of Ia + cells.