Footpad swelling response was used to measure the alloantigenicity of epidermal cells (ECs) in delayed-type hypersensitivity (DTH). Strong footpad swelling was observed 3 h after the challenge, and it continued for 48 h after the challenge. Genetical incompatibility between the recipients and the ECs was required to induce significant footpad swelling. H-2 or non-H-2 incompatibility between mice and ECs in the sensitization phase sufficed to develop significant footpad swelling. Incompatibility caused by point mutation in the A region induced strong responses when B6.C-H-2bm12 mice were immunized with B6/J ECs, but the disparity in immunoglobulin h (Igh) allotype genes was insufficient. H-Y antigen on ECs could also elicit the DTH response. Semiallogeneic F1-derived ECs sensitized the parental recipients. The responses were successfully transferred by immune lymph node cells, but not by immune sera. Treatment of these immune lymph node cells with monoclonal antibodies plus complement revealed that the cells responsible for DTH transfer were Lyt-1+2-, Ia- T cells.