Nontuberculous mycobacteria (NTM) are intracellular pathogens that elicit a specific T-cell response characterized by the production of proinflammatory cytokines, including interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-12. However, little information exists regarding the levels of specific cytokines in patients with NTM lung disease. Therefore, we compared cytokine production in peripheral blood mononuclear cells (PBMCs) from patients with NTM lung disease with that in PBMCs from healthy controls. Pro- and anti-inflammatory cytokine production was measured by enzyme-linked immunosorbent assay in the PBMCs of 29 patients with NTM lung disease and 15 healthy controls. Phytohemagglutinin (PHA)-induced IFN-gamma production and lipopolysaccharide (LPS)-induced production of TNF-alpha and IL-12p40 were significantly lower in the PBMCs of patients with NTM lung disease than in those of the healthy controls. The production of these cytokines did not differ significantly between patients infected with Mycobacterium avium complex (MAC) and those infected with Mycobacterium abscessus; however, IL-10 production was lower in patients infected with M. abscessus than in those infected with MAC. Decreased IFN-gamma, TNF-alpha, and IL-12 production may be associated with host susceptibility to the development of MAC and M. abscessus lung disease.