Anew B70 variant, B*1580, has been identified in a Swiss Caucasoid blood donor. Sequencing of exons 2 and 3 revealed that the HLA-B*1580 differs from its closest matching allele B*1518 by two substitutions in exon 3, leading to two amino acid changes, threonine to isoleucine and leucine to isoleucine at codons 94 and 95, respectively. The complete human leukocyte antigen type of the donor is: A*2402, A*2601; B*5101, B*1580; Cw*0704, Cw*1402/05; DRB1*0801, DQB1*0402. The B*1580 is a new member of the B70 cluster, characterized by the SEE motif at positions 24, 45, and 46 in the alpha1-domain. Substitutions at codons 94 and 95, also found in some B62 and B75 alleles, do not appear to interfere with the B70 serological reactivity. Based on sequence similarity and linkage with Cw*0704, the rare alleles B*1509, B*1529, B*1564, and B*1580 are possibly derived from the B*1518 haplotype.