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Objectives: With the current repertoire of immunosuppressants available, the results of organ transplantation are now very good in the short term. However, many grafts continue to be lost in the long term because of chronic rejection. This study examined the effect of kidney transplantation against a positive flow cytometry crossmatch (FCXM) on the subsequent development of chronic rejection and graft failure., Methods: We examined 187 primary renal transplantations performed at our institution between 1993 and 1996. All of these patients had a negative cytotoxicity crossmatch. All had a pretransplant FCXM, and patients were divided according to the results of the FCXM into three categories: FCXM negative, FCXM class I positive, and FCXM class II positive., Results: We found that a positive FCXM at the time of transplantation was strongly associated with the ultimate development of chronic rejection. In FCXM-negative individuals, 16.9% developed chronic rejection compared with 80% of those with an HLA class I (T and B-cell) reaction and 40.9% of those with a class II (B-cell-only) reaction (P <0.001). The 3-year graft survival rate was 93% for FCXM-negative patients compared with 86% for FCXM class II positive and 80% for FCXM class I positive patients (P = 0.001)., Conclusions: A strong association between a positive FCXM and subsequent development of chronic rejection was identified. This finding raises the possibility that more aggressive treatment of patients with a positive FCXM might ultimately result in a lower incidence of chronic rejection and improve overall graft survival.