The pathway involving interferon-gamma and interleukin (IL)-12 plays an important role in host defense against mycobacterial infections. Recent studies have indicated that IL-12 receptor beta1 (IL-12Rbeta1) gene polymorphisms are associated with susceptibility to pulmonary tuberculosis. However, there have been no reports of an association between IL-12Rbeta1 gene polymorphism and lung disease caused by nontuberculous mycobacteria (NTM). The present study involved 128 patients with the nodular bronchiectatic form of NTM lung disease (75 patients with Mycobacterium avium-intracellulare complex infection and 53 patients with Mycobacterium abscessus infection) and 240 healthy controls. Single nucleotide polymorphisms of the IL-12Rbeta1 gene at positions +705A/G, +1158T/C, and +1196G/C were determined by direct sequencing of polymerase chain reaction products. Comparisons of the NTM lung disease patients with healthy controls did not identify any significant differences in relation to the genotype, allele, and haplotype frequencies of the IL-12Rbeta1 +705A/G, +1158T/C, and +1196G/C polymorphisms. These IL-12Rbeta1 gene polymorphisms do not appear to be responsible for host susceptibility to NTM lung disease, at least in this Korean population.