Interferon-gamma (IFN-gamma) is crucial for host defense against mycobacterial infections. Recent studies have indicated that IFN-gamma and IFN-gamma receptor 1 (IFN-gammaR1) gene polymorphisms are associated with susceptibility to pulmonary tuberculosis. The aim of this study was to test the hypothesis that IFN-gamma and IFN-gammaR1 gene polymorphisms influence susceptibility to lung disease caused by non-tuberculous mycobacteria (NTM). Seventy-six patients with the nodular bronchiectatic form of NTM lung disease (37 patients with Mycobacterium avium complex infection and 39 patients with Mycobacterium abscessus infection) and 80 controls were included. Polymorphisms of the IFN-gamma gene at position +874 were determined by the amplification refractory mutation system (ARMS) polymerase chain reaction assay and IFN-gammaR1 gene at positions -611, -270, -56 and +95 was genotyped by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry using genomic DNA. IFN-gammaR1 -270 and +95 polymorphisms were not present in any of the patients or controls. The patients with NTM lung disease showed no significant difference from controls in genotype and allele frequencies of the IFN-gamma +874 and IFN-gammaR1 -611 and -56 polymorphisms. The IFN-gamma +874 and IFN-gammaR1 -611 and -56 polymorphisms do not appear to be responsible for host susceptibility to NTM lung disease, at least in the Korean population.