An important question in local immune regulation in the skin is how keratinocytes at inflammatory sites can modify a local T-cell response to antigens introduced via the skin. In the present study we investigated the effects of rat epidermal cells obtained from the site of a tuberculin reaction, on the proliferative response of a syngeneic purified protein derivative (PPD)-specific CD4+ T-cell line. Epidermal cell suspensions from the tuberculin-reactive ears contained 23-37% cells expressing class II transplantation antigens as judged by immunocytochemistry compared with 2-3% in normal epidermis. When comparing the capacity of these two different epidermal cell populations to induce a PPD-specific T-cell response in vitro, it was found that the PPD-reactive epidermal cells induced a lower T-cell response than did normal epidermal cells. This discrepancy cannot be explained by an infiltration of inflammatory cells into the epidermis of tuberculin-reactive ears. Our data indicate that epidermal cells modified during a delayed-type hypersensitivity reaction in vivo may suppress an antigen-specific T-cell proliferation.