Patients with pulmonary Mycobacterium avium complex (MAC) infection occasionally have neither past histories of pulmonary diseases nor underlying immunodeficiency conditions. Therefore, we hypothesized that MAC may be linked with a disease-susceptibility gene and determined human leukocyte-associated antigens (HLA) in patients with pulmonary MAC infection. HLA phenotypes were tested in 59 patients with pulmonary MAC infection, and diagnosed according to the criteria of the American Thoracic Society. Data of a Japanese population reported at the Tenth Japan HLA Workshop were used as a control. HLA-A33 (28.8% versus 12.5%, p = 5 x 10(-)(4)) and HLA-DR6 (50.8% versus 20.2%, p = 5 x 10(-)(8)) antigen frequencies in patients with MAC were significantly increased compared with those of the control population. Frequency of a haplotype A33-B44-DR6 in the MAC patients was also significantly increased compared with those of the control population (23.7% versus 4.2%; p = 3 x 10(-)(9)). These data suggest that development of pulmonary MAC infection is associated with specific HLA in a Japanese population.