The mycobacterial response was evaluated for patients with Mycobacterium avium-intracellulare complex (MAC) bacteremia treated with a quadruple regimen of rifabutin, clofazimine, isoniazid, and ethambutol. Mycobacteremia was cleared in 22 of 25 patients who received this regimen, and 18 patients experienced complete resolution of symptoms associated with MAC infection. All of the patients were immunodeficient, with a mean CD4 cell count at the time of diagnosis of MAC infection of 54.7 +/- 54.6 cells/microliters. All MAC isolates were resistant to clofazimine, isoniazid, and ethambutol. Sixteen of 24 isolates were resistant to rifabutin. Improved results of treatment may be related to the use of a higher dose of rifabutin (300-600 mg/day) compared with other studies (150-300 mg/day), earlier diagnosis and institution of treatment, and synergy between rifabutin and ethambutol. The quadruple regimen used in this study appears effective in clearing mycobacteremia and in ameliorating symptoms of infection.