We studied the quantity of Langerhans cells in 36 patients with cervical human papillomavirus (HPV) infection. Significantly fewer Langerhans cells (p < 0.05) were found in patients with compared to those without DNA tetraploidy. Similarly, patients positive for HPV 16/18 DNA by in situ hybridization or antipeptide IgA antibodies to HPV 18 tended to have fewer Langerhans cells than those negative for HPV 16/18 DNA or IgA antibodies. Our results suggest that depletion of Langerhans cells is associated with productive HPV 16/18 infection in the cervical epithelium.