Since the initial presentation by Kissmeyer-Nielsen and colleagues  and later by Patel and Terasaki , it has been accepted that renal transplantation should not be performed in the presence of cytotoxic alloreactive antibodies of the IgG fraction performed at room temperature against HLA Class I [Braun 1989] antigens. Such antibodies are feared to induce hyper-acute or accelerated rejection because of the presence of HLA Class I antigens on kidney cells. For this reason, the microlymphocytotoxicity crossmatch (XM test: recipient serum reacted against donor lymphocytes as surrogate for HLA antigens) is now universally used before transplantation [Ting 1983]. A positive XM performed against the recipient T lymphocyte at room temperature after treatment of recipient serum with dithiothreitol (DTT), an agent that removes immunoglobulin M, denotes the presence of cytotoxic alloreactive IgG antibodies against the potential donor HLA class I antigen. Herein, we present the case of a patient who developed positive XM test of the IgG isotype against HLA Class I of the donor antigens performed at room temperature seven days after she received a kidney allograft from her daughter. Although the development of a positive XM was associated clinically with acute rejection, the patient responded remarkably well to anti-rejection therapy and maintained excellent graft function thereafter. Thus, strategies to identify the role played by the different IgG isotypes determined against HLA Class I antigens and their relation to irreversible rejection are needed to differentiate between those potential kidney recipients who may benefit from kidney transplantation in the presence of innocent warm IgG subclass antibodies reactive against HLA Class I antigens and those patients who may not.