Human immunodeficiency virus (HIV) is known to infect Langerhans cells, but controversy still exists about the occurrence of HIV-infected Langerhans cells in the skin of HIV-infected individuals and about the density of epidermal Langerhans cells during the course of HIV disease. In this study, epidermal Langerhans cell population densities were analyzed quantitatively in serial biopsies from two burn patients acquired over an 11-y period following infection with HIV from transfusions received during their acute treatment. At each biopsy time point, the density of epidermal Langerhans cells and the proportion that were infected with HIV were analyzed by immunostaining. In both patients, skin grafts were slow to repopulate with Langerhans cells and did not attain normal Langerhans cell densities until about 2 y after grafting. Thereafter, Langerhans cell densities remained within normal limits with the exception of six biopsies at random times that showed a supernormal number of epidermal Langerhans cells. HIV-infected Langerhans cells were first detected at about 2 y post-infection and comprised about one-third of the Langerhans cell population. At subsequent times, HIV p24-stained Langerhans cells were identified in most biopsies and typically constituted about one third to one half of the total Langerhans cell population. The findings show that HIV-bearing Langerhans cells constitute a significant proportion of the epidermal Langerhans cell population over long periods of asymptomatic disease but are unevenly distributed throughout the skin. Normal population densities of epidermal Langerhans cells are maintained for years, although transient increases may occur randomly.