This study looked the selection of resistant mutants in Mycobacterium avium-intracellulare during antibiotic treatment. The mutant prevention concentration (MPC) of 20 Mycobacterium avium and 12 Mycobacterium intracellulare isolates was determined. Fifty percent of Mycobacterium avium strains had MPC (MPC50) values lower than 16, 64, 40, 55 and 60 mg/L for rifabutin, rifampicin, ciprofloxacin, levofloxacin and moxifloxacin, respectively. In the case of Mycobacterium intracellulare, 50% had MPC (MPC50) values below 60, 30, 35, 16, 2.5 and 14 mg/L for linezolid, rifabutin, levofloxacin, gatifloxacin, moxifloxacin and clarithromycin, respectively. The high capacity for selecting resistant mutants of all the antibiotics studied emphasises the need to restore the immune system if necessary and to administer combined treatments in order to cure patients.