We examined the functional roles of HLA-DR+ keratinocytes which were induced in vivo from tuberculin reactive skin. At 4 days after intradermal PPD injection, about 80% of keratinocytes obtained from the tuberculin reactive area expressed DR antigens. In 14 of 18 individuals examined, PPD-pulsed DR+ keratinocyte fraction induced autologous T-cell proliferation. The proliferative response was PPD-dependent, antigen specific; it depended upon DR expression by the keratinocyte fraction, because it did not occur in the presence of the PPD-nonpulsed DR+ keratinocyte fraction and was completely blocked by mouse monoclonal antibody to HLA-DR. However, the antigen-presenting capacity of the DR+ keratinocyte fraction appeared to be less than that of monocytes or the DR+ epidermal cell fraction. The DR+ keratinocyte fraction was also able to stimulate allogeneic T-cell DNA synthesis, but the DR- keratinocyte fraction could not. The possible influences of contaminant Langerhans cells and mononuclear cells in the DR+ keratinocyte fraction were considered to be unlikely. These results suggest that DR+ keratinocytes, which are induced in vivo, can both present the antigen to autologous T cells and stimulate allogeneic T cells.