Serious infections caused by the Mycobacterium avium complex (MAC) have been increasingly recognized over the last three decades. However, the epidemic of the acquired immunodeficiency syndrome (AIDS) has increased interest in these infections. Disseminated mycobacterial disease is common in patients with AIDS, and MAC is the predominant bacterial isolate. Indeed, at UCLA Medical Center, MAC organisms are now the predominant isolates in both AIDS- and non-AIDS-associated mycobacterial disease. MAC lung infections have been difficult to treat. Complex regimens employing four to six drugs are not clearly effective and are usually associated with considerable toxicity. Treatment of MAC infections in patients with AIDS has been particularly frustrating, and evidence that treatment can either eradicate disease or prolong life is limited. MAC organisms are invariably resistant to traditional antituberculosis medications. We have examined a variety of other compounds, and our findings, based on both in vitro and animal-model studies, have identified drugs which, when used in combination, are potentially of therapeutic utility.