We treated 39 elderly human immunodeficiency virus-noninfected patients with Mycobacterium avium complex and/or Mycobacterium abscessus lung disease with azithromycin (600 mg daily), given initially as monotherapy. Adverse events occurred in 33 of 39 patients (85%) receiving azithromycin alone, most commonly gastrointestinal (GI) symptoms (32 of 39, or 82%) and hearing impairment (10 of 39, or 26%). Twenty-four of 39 patients (62%) required a lower dose or withdrawal of the drug. The mean serum level in patients who required a dose reduction because of hearing impairment was 0.8 +/- 0.4 microg/mL, and that in patients whose reduction was necessitated by GI symptoms was 0.7 +/- 0.4 microg/mL; in comparison, the mean serum level was 0.3 +/- 0.16 microg/mL in patients with no adverse events (P = .004 and .003, respectively). Decreasing the daily dose to 300 mg resulted in resolution of most adverse events. Serum levels with monotherapy were comparable to levels after the addition of other antituberculous drugs that included rifampin or rifabutin. Thus, a 300-mg rather than 600-mg daily dose of azithromycin is better tolerated by elderly patients, and serum levels appear unaffected by other antituberculous agents, including rifampin.