The activity of TLC G-65 (a liposomal gentamicin preparation), alone and in combination with rifapentine, clarithromycin, clofazimine and ethambutol, was evaluated in the beige mouse (C57BL/6J--bgj/bgj) model of disseminated Mycobacterium avium infection. TLC G-65 was found to be more active than amikacin. The combination of rifapentine and TLC G-65 was more active than either agent alone. The activity of clarithromycin in combination with TLC G-65 was similar to that of either agent alone. Clofazimine improved the activity of TLC G-65 with respect to the spleen, while ethambutol improved the activity with respect to the liver. Clofazimine and ethambutol enhanced the activity of TLC G-65 against bacteria in the lungs. TLC G-65 in combination with rifapentine appears to be an attractive regimen for the treatment of infections caused by bacteria in the M. avium complex.