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We determined HLA-A, -B, and -DR allele frequencies in kidney transplant recipients in relation to graft survival. Most recipients and donors were from African descent. The frequency of HLA-A30 was somewhat increased in recipients who rejected the graft. The frequency of HLA-B42 was significantly (P=0.002) increased in recipients who rejected the graft. Similar results were found for the HLA-DR3 allele; however, this effect was diminished when B42-, DR3+ individuals were analyzed. We further investigated the effect on transplant outcome of a unique African haplotype A30, B42, DR3, and of segments thereof, which have a high frequency in the local population. Log-rank analysis revealed that the negative effect on transplant outcome was least in A30-, B42+ recipients (P=0.417) and most pronounced in A30+, B42+ patients (P=0.006). We postulate that the negative effect on transplant outcome may reside in the A30, B42 segment of chromosome 6 and may be caused by a stronger than average immunoregulatory gene.