We have determined IL-10 promoter genotypes of five single-nucleotide polymorphisms (SNPs): TÀ3575A, AÀ2849G, CÀ2763A, -AÀ1082G and CÀ819T. The haplotype frequencies were defined in healthy subjects compared to leprosy patients, and analyzed for their occurrence in multi-(MB) vs paucibacillary (PB) as severe and mild forms of leprosy, respectively. Haplotypes defined by three SNP positions (À3575, À2849 and À2763) captured significant differences between controls and patients (P ¼ 0.04). The haplotype carrying À3575A, À2849G and À2763C was associated with resistance to leprosy and to the development of severe forms of the disease using either a binomial (controls vs cases, P ¼ 0.005, OR ¼ 0.35, CI ¼ 0.13-0.91) or ordinal (controls vs PB vs MB, P ¼ 0.006, OR ¼ 0.32, CI ¼ 0.12-0.83) model. By contrast, the IL-10 haplotype À3575T/ À2849A/À2763C was found to be associated with susceptibility to leprosy per se (P ¼ 0.027, OR ¼ 2.37, CI ¼ 1.04-5.39), but not leprosy type. The data suggest that the IL-10 locus contributes to the outcome of leprosy.