Dantu is a rare antigen of the human MNSs blood group system carried by a hybrid glycophorin on the erythrocyte membrane. To delineate its structure and relationship to alpha and delta glycophorins at the genomic level, we analyzed DNA from a three-generation family, in which both the presence of Dantu and Mi-III (another rare MNSs antigen) and the absence of delta glycophorin were seen. Three gross alterations in the gene cluster correlated with the observed phenotypes. Differential hybridization, secondary restriction analysis, and sequence-specific oligonucleotide probing established that Dantu glycophorin is encoded by a distinct hybrid gene derived from fusion of delta and alpha genes. The junction point of the Dantu gene was assigned to the region spanning codons 31-39 of delta and codons 72-79 of alpha genes. Dosage quantitation suggested that Dantu gene is duplicated and tandemly arranged. Identification of delta gene deletion disclosed the molecular basis for the absence of delta glycophorin in two Dantu and Mi-III double heterozygotes. The DNA inheritance pattern together with DNA typing of MN blood groups verified the genotypes and established that the duplicated Dantu hybrid gene is linked to alpha M gene as well as a delta gene deletion. The origin of such a haplotype in a segment of Black population would require two recombination events via either unequal homologous crossing-over or gene conversion.