Mycobacterium avium complex infections, common in patients with AIDS as either pulmonary or disseminated disease, are infrequent in patients without AIDS. Participants were 45 HIV-negative patients with lung disease and positive sputum cultures for M avium; 10 had documented immunocompromise, and 24 had preexisting lung disease. Clarithromycin dosage was 500 to 2,000 mg daily (mean +/- SD = 1,633 +/- 432 mg). The drug was administered either alone (n = 14) or in combination with rifampin (n = 8), aminoglycoside (n = 1), quinolone (n = 10), clofazimine (n = 18), isoniazid (n = 5), ethambutol (n = 9), pyrazinamide (n = 1), or minocycline (n = 6). At 3 months, 36 patients among 39 bacteriologically assessed had negative sputum cultures, 3 had positive culture, 3 were dead, and 3 discontinued treatment. At the end of treatment, 32 patients remained negative, 7 were positive. The success rate was 15 of 22 (64%) in patients previously treated with antimycobacterial drugs for M avium disease and 17 of 23 (74%) in new patients. Adverse effects included mild hearing loss (n = 4), increase in liver enzyme levels (n = 5), and gastrointestinal pain (n = 10, two of whom had to stop treatment). Patients stopped treatment after 300 +/- 186 days due to side effects (3), death (4), or the patient's (5) or physician's decision (33). During the follow-up, one patient suffered a relapse with peripheral lymph nodes. A daily dose of 30 mg/kg of clarithromycin in the treatment of M avium infections appears to be effective and safe. Concomitant drug therapy should be assessed for its ability to prevent relapse.