Current treatments of disseminated infection caused by the Mycobacterium avium-M. intracellulare complex (MAC) are generally ineffective. Liposome-mediated delivery of antibiotics to MAC-infected tissues in vivo can enhance the efficacy of the drugs (N. Düzgüneş, V. K. Perumal, L. Kesavalu, J. A. Goldstein, R. J. Debs, and P. R. J. Gangadharam, Antimicrob. Agents Chemother. 32:1404-1411, 1988; N. Düzgüneş, D. A. Ashtekar, D. L. Flasher, N. Ghori, R. J. Debs, D. S. Friend, and P. R. J. Gangadharam, J. Infect. Dis. 164:143-151, 1991). We investigated the therapeutic efficacies of liposome-encapsulated streptomycin and ciprofloxacin against growth of the MAC inside human peripheral blood monocyte/macrophages. Treatment was initiated 24 h after infection of macrophages with the MAC and stopped after 20 h, and the cells were incubated for another 7 days. The antimycobacterial activity of streptomycin was enhanced when the drug was delivered to macrophages in liposome-encapsulated form, reducing the CFU about threefold more than the free drug did throughout the concentration range studied (10 to 50 micrograms/ml). With 50 micrograms of encapsulated streptomycin per ml, the CFU were reduced to 11% of the initial level of infection. Liposome-encapsulated ciprofloxacin was at least 50 times more effective against the intracellular bacteria than was the free drug: at a concentration of 0.1 microgram/ml, liposome-encapsulated ciprofloxacin had greater antimycobacterial activity than the free drug at 5 microgram/ml. With liposome-encapsulated ciprofloxacin at 5 micrograms/ml, the CFU were reduced by more than 1,000-fold at the end of the 7-day incubation period, compared with untreated controls. These results suggest that liposome-encapsulated ciprofloxacin or other fluoroquinolones may be effective against MAC infections in vivo.