PROJECT DESCRIPTION Clofazimine is an orphan antibiotic drug that is no longer available through pharmacies in the United States. It is approved for the treatment of Mycobacterium leprae (leprosy) infections. Clofazimine has been used for many years off-label against other Mycobacterium, including Mycobacteria avium complex (MAC) lung disease, an increasingly prevalent infection in older Americans. The U.S. Food and Drug Administration currently oversees clofazimine use to treat MAC lung disease through a special investigational drug access program. However, to date, there is little understanding of the benefits and risks of clofazimine when used to treat MAC lung disease. Accordingly, we have developed a randomized, placebo-controlled clinical trial to assess the clinical efficacy and safety of clofazimine. To be eligible, patients must have MAC lung disease, positive sputum cultures for MAC, and not currently taking antibiotics for MAC. Eligible patients (102 total enrolled) will be randomly given either clofazimine or placebo for 6 months, and followed closely by their treating physician. The percentage of patients who become culture negative in each group will be compared, as we suspect patients treated with clofazimine will be more likely to become culture negative. We will also measure the safety of clofazimine as well as other potential benefits of the therapy including changes in lung function and quality of life.