Mice homozygous for three different recessive mutations known to cause pleiotropic defects in the immune system and in the skin were used to evaluate the relationship between the classical immune system and dendritic epidermal cell populations. Numbers of Langerhans cells (LCs) and Thy-1 + dendritic cells (Thy-1 + DEC) were determined using indirect immunofluorescence microscopy of epidermal whole mounts taken from viable motheaten (me~), nude (nu), and rhino (rh hr) mice. All mutants were maintained on the C57BL/6J strain background and were compared with their respective littermate normal controls. Viable motheaten mice had normal numbers of LCs at 1 month of age. However, by 8 weeks of age, LC density had decreased threefold. Nude and rhino mice had normal numbers of LCs at all ages tested. There was no significant effect of the viable motheaten mutation on numbers of Thy-I+DEC. Although nude mice showed normal numbers of Thy-1 + DEC at 1 month of age, these athymic mice had a threefold decrease in numbers of such cells by 6 months. In contrast to the reduced numbers of Thy-1 +DEC seen in nude mice, rhino mice showed a four-to fivefold increase in the numbers of these epidermal cells at all ages tested. These findings suggest new mouse models for investigating the development, regulation, and biological properties of epidermal dendritic cell populations.