Host factors have been shown to play a significant role in the susceptibility to and clinical outcome of leprosy. Here, we analyze polymorphisms of the gene encoding ficolin-2 (FCN2), which is a soluble pattern-recognition molecule. A total of 158 patients with leprosy and 210 healthy control subjects from Brazil were investigated. Polymorphisms in the promoter and exon 8 of FCN2 were assessed by DNA sequencing. The distribution of functional FCN2 haplotypes amongpatients was significant different from that among the control subjects (P = .004). These results unveil an immunogenetic role for ficolin-2 in the host response against M. leprae.