The survival rate in patients with AIDS who have CD4+ cell counts < 75 cells/microliter is increasing because of improved preventive and treatment strategies for opportunistic infections and also because of the efficacy of antiretroviral drug treatment. These patients are at high risk of developing disseminated Mycobacterium avium-intracellulare (MAC) disease, which decreases both quality of life and life expectancy. Measures aimed at preventing MAC contamination are largely ineffective in decreasing the incidence of disseminated MAC disease in patients with AIDS, because of the large natural reservoir of MAC. Chemoprophylaxis is superior to early bacteriological diagnosis as a preventive strategy, and it is preferable to wait for the appearance of symptoms of disseminated MAC disease before a curative treatment is initiated. Well-conducted studies of clarithromycin or rifabutin monotherapy as chemoprophylaxis have demonstrated a decrease in the incidence of disseminated MAC disease, as well as an increase in quality of life and survival. Clarithromycin, azithromycin and rifabutin have all been shown to be effective as prophylaxis against disseminated MAC disease. Although some combinations of drugs have been shown to be more effective than monotherapy in preventing disseminated MAC disease, these regimens are more costly and have less favourable tolerability profiles than single-agent treatment. In conclusion, chemoprophylaxis is the most effective preventive strategy against disseminated MAC disease and has been shown to improve quality of life and to decrease the risk of death associated with this disease in AIDS patients.