The effect of flow cytometry crossmatches on clinical outcome was studied retrospectively in two groups of immunologically well-documented patients who had received transplants with a negative complement-dependent cytotoxicity crossmatch. The first group consisted of 114 consecutive renal allograft recipients, and the second group consisted of 76 immunologically at-risk recipients. Flow cytometry crossmatches were performed with current and historic sera. In group 1, positive flow cytometry (FC) crossmatches were shown in 15/114 (13%) recipients. Rejection occurred in 8/15 (53%) FC-positive versus 41/99 (41%) FC-negative recipients. The 1-year graft survival rate was 80% for FC-positive patients and 87% for FC-negative patients. Sixty-seven patients were nonsensitized patients; 4 of them had a positive FC crossmatch but no rejection episodes, graft loss, or patient loss. Of 47 retransplanted and/or sensitized recipients, 11 had a positive FC crossmatch. Rejection treatment was needed in 8/11 (73%) FC-positive patients compared with 19/36 (53%) FC-negative patients. Their 1-year graft survival rates were 73% and 81%. None of these differences reached statistical significance. Group 2 consisted of 76 at-risk recipients; 37 were retransplant patients and 39 were sensitized first-transplant patients. Twenty-one (28%) patients showed a positive FC crossmatch. Rejection episodes did not differ between the FC-positive (48%) and FC-negative patients (46%). There was no difference in 1-year graft survival rate (76% vs. 80%) or in 1-year patient survival rate (100% vs. 95%). We conclude that FC crossmatches in our patient group are not superior to the classical complement-dependent cytotoxicity crossmatches with regard to clinical outcome. On the contrary, transplantation with a mandatory negative FC crossmatch would have excluded 28% of the recipients from transplantation, who in fact are doing well.