Circulating antibodies reacting with donor lymphocytes, increasingly found in patients awaiting a kidney graft, are a cause of transplantation delays. Some of these antibodies may not be detrimental to the graft, and their recognition could be beneficial for the treatment of immunized patients. In this chapter, we report on a prospective study of 138 cases of kidney transplantation performed against a positive crossmatch (CM) on donor B lymphocytes. In all cases, a negative reaction was required on donor T lymphocytes using recipient pregraft sera. Sera of 36.3% and 43.6% of first and second-graft recipients, respectively, were also reactive on unseparated donor total lymphocytes. First grafts performed against donor B lymphocytes reacted like those with a negative CM in terms of graft survival, rejection incidence, and graft function in the first year. Surprisingly, an uncommonly high rate of success was observed in second grafts performed against a positive donor B-lymphocyte CM as compared to those with a negative B-cell CM (93.5% vs 62.8% graft survival at 2 years; p less than 0.05). In addition, these patients had a decreased rejection incidence and significantly better graft function (p less than 0.05) as compared to those grafted with a negative B-lymphocyte CM. In the 43.6% who also had a positive CM on total donor lymphocytes (negative CM on donor T cells) and would not have been grafted according to common CM policy, actuarial graft survival was 86.7%. Our results within the given procedure show that transplantation against a positive donor B-cell CM is not detrimental to a first graft.(ABSTRACT TRUNCATED AT 250 WORDS)