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A novel HLA-B∗39 variant, found in an African patient with sickle cell anemia undergoing bone marrow transplantation is described. Initially suspected by inconsistent serological typing (B-blank, Bw6), then recognized by PCR-SSP, and finally characterized by nucleotide sequencing, this novel allele is designated HLA-B∗3916. It differs from HLA-B∗3910 by a point mutation (G to C) at position 17 of exon 3 causing glutamine to histidine change at codon 96 of α 2 domain, a conserved position among HLA class I alleles. cDNA sequence analysis further revealed the presence of both normally and abnormally spliced mRNA species in established cell lines. The abnormal species correspond to partial truncation of exon 3 presumably due to the nucleotide change in exon 3, which constitutes a new consensus acceptor splice site within this exon. We postulate that the observed blank is essentially the consequence of qualitative change in a critical region of this novel antigen as abnormal mRNA species are relatively less abundant than normal species. Because the residue 96 of the HLA class I heavy chain is directly involved in interaction with α 2 m, another interesting possibility is that an aminoacid change in this position would perturb such interaction and consequently could affect the serological specificity of B∗3916, or its expression or both.