Mycobacterium avium is abundant in the environment. It has four subspecies of three types: the human or porcine type, M. avium subsp. hominissuis; the bird type, including M. avium subsp. avium serotype 1 and serotype 2, 3 (also M. avium subsp. silvaticum); and the ruminant type, M. avium subsp. paratuberculosis. We determined the subspecies of 257 M. avium strains isolated from patients at the M.D. Anderson Cancer Center from 2001 to 2010 and assessed their clinical significance. An assay of multiplex PCR was used for the typing. Results showed M. avium subsp. hominissuis to be most common (n ؍ 238, 92.6%), followed by M. avium subsp. avium serotype 1 (n ؍ 12, 4.7%) and serotype 2, 3 (n ؍ 7, 2.7%). No strains of M. avium subsp. paratuberculosis were found. Of the 238 patients with M. avium subsp. hominissuis, 65 (27.3%) showed evidence of definite or probable infections, mostly in the respiratory tract, whereas the rest had weak evidence of infection. The bird-type subspecies, despite being infrequently isolated, caused relatively more definite and probable infections (10 of 19 strains, 52.6%). Overall, women of 50 years of age or older were more prone to M. avium infection than younger women or men of all ages were. We therefore conclude that M. avium subsp. hominissuis is the dominant M. avium subspecies clinically, that the two bird-type subspecies do cause human infections, and that M. avium infects mainly postmenopausal women. The lack of human clinical isolation of the ruminant type subspecies may need further investigation. N ontuberculous mycobacteria are ubiquitous in the environment and can cause significant disease in animals and humans (1-5). Mycobacterium avium and Mycobacterium intracellulare were the two original main species belonging to the M. avium-M. intracellulare complex (MAIC). M. avium is an important opportunistic pathogen that causes respiratory tract, lymph node, and, occasionally, soft tissue infections in healthy immunocompetent individuals (6, 7). Moreover, secondary infections with M. avium have gained increased attention over the decades due to the longevity of the immunocompromised population, i.e., individuals living with HIV and AIDS, and the administration of immunosuppressive chemotherapeutics in cancer patients (8).With the development of new molecular identification methods, M. avium has been further subdivided into four major subspecies: M. avium subsp. avium, M. avium subsp. paratuberculosis, M. avium subsp. silvaticum, and M. avium subsp. hominissuis (9, 10), each with distinct pathogenic characteristics and host preference and all considered possible zoonoses. These M. avium subspecies are considered to be a broad group, particularly M. avium subsp. avium and M. avium subsp. paratuberculosis as independently evolved pathogenic clones (9, 10).