The mRNA for the Duffy blood group antigen, the erythrocyte receptor for the Plasmodium vivax malaria parasite, has recently been cloned and shown to encode a widely expressed chemokine receptor. Here, we show that the Duffy antigen/chemokine receptor gene (DARC) is composed of a single exon and that most Duffy–negative blacks carry a silent FY^*B allele with a single T to C substitution at nucleotide −46. This mutation impairs the promoter activity in erythroid cells by disrupting a binding site for the GATA1 erythroid transcription factor. With the recent characterization of the FY^*A and FY^*B alleles, these findings provide the molecular basis of the Duffy blood group system and an explanation for the erythroid–speeific repression of the DARC gene in Duffy–negative individuals.