Interleukin-13 (IL-13) is a cytokine involved in Th2 immune response, which plays a role in susceptibility to infection by extracellular parasites as well as complex diseases of the immune system such as asthma and allergies. To determine the pattern of genetic diversity at the IL13 gene, we sequenced 3950 bp encompassing the IL13 gene and its promoter in 264 chromosomes from individuals originating from East and West Africa, Europe, China and South America. Thirty-one single-nucleotide polymorphisms (SNPs) arranged in 88 haplotypes were indentified, including the nonsynonymous substitution Arg130Gln in exon 4, which differs in frequency across ethnic groups. We show that genetic diversity and linkage disequilibrium (LD) are not evenly distributed across the gene and that sites in the 5′ and 3′ regions of the gene show strong differentiation among continental groups. We observe a divergent pattern of haplotype variation and LD across geographic regions and we identify a set of htSNPs that will be useful for functional genetic association studies of complex disease. We use several statistical tests to distinguish the effects of natural selection and demographic history on patterns of genetic diversity at the IL13 locus. © 2005 Nature Publishing Group. All rights reserved.