Using HLA serology, we detected a new variant of HLA-B44- B44BO- in two families. This antigen reacts with B44 antisera and is negative with over one-third of B12 (B44, B45) sera but reacts with 50% antisera with a B62 component, especially if they contain anti-B57. The variant, B*4408, differs from the common B*4402 by 4 nucleotide substitutions in exon 2: 193, 206 and 209, which produce changes in the the alpha 1 domain at positions 41, 45 and 46 (TKE in B*4402 and AMA in B44BO); and nucleotide 213, a silent substitution. At each of these positions, B*4408 is identical to B*46 B*57 and may B*15 alleles. As anticipated from its predicted iso-electric point (5.71), one-dimensional isoelectric focusing studies showed that B44BO focuses at the same position as B*4402. The sequence and serological reactivity of this rare antigen allowed the identification of two likely epitopes shared by two different groups of HLA-B antigens.