Summary: Current methods of measuring allograft responses in vivo are largely subjective, qualitative or cumbersome.The increase in weight undergone by the popliteal lymph node following the injection of allogeneic cells into the foot‐pad has been explored as a possible alternative assay.Lymph node enlargement was found to be an immunologically specific response; invariably present where challenge cells bore allo‐antigens not shared by the recipient; absent in irradiated, tolerant, or syngeneic hosts and specifically altered by prior sensitization. It occurred independently of donor cell proliferation.The kinetics of lymph node enlargement in normal recipients were similar in all Ag‐B disparate strain combinations tested. Peak lymph node weights were invariably found 4 days after challenge. The degree of enlargement was precisely related to the number of challenge cells and was much greater in Ag‐B disparate than in Ag‐B identical combinations. The magnitude of the response to a given dose of antigen varied with the strain of the recipient and was highly reproducible.The technique is economical of animals and time and is extremely simple to perform. It fulfils most of the requirements for an ideal quantitative allograft assay.