Interleukin (IL)-12 plays a pivotal role in cell-mediated immunity to Mycobacterium tuberculosis infection. We tested the association between a biallelic single-nucleotide polymorphism in the 3' untranslated region (UTR) of IL-12B and human susceptibility to tuberculosis (TB), in a population-based case-control study of adult patients with TB from 2 ethnicities, African American and white, and in a family-based transmission/disequilibrium study of 60 informative families with at least 1 pediatric patient with TB and 1 heterozygous parent. Our results suggest that IL-12B 3' UTR has no effect or has a negligible effect on human susceptibility to TB.