In order to identify novel single nucleotide polymorphisms (SNPs), we sequenced a 940 bp region of the 5' flanking region of the IL-6 gene in 63 normal African-Americans. We identified a biallelic (G/C) SNP at position -573 relative to the transcription start site (-573C allele frequency 0.095). This SNP, together with SNPs at -598 and -174, allows identification of five probable haplotypes. Haplotypes containing the -174C allele, which has been associated with lower plasma IL-6 levels, were uncommon (4%). These haplotypes may influence IL-6 gene transcription and thus may contribute to racial differences in the prevalence of inflammatory diseases.