The increasing incidence of drug-resistant Mycobacterium tuberculosis necessitates therapeutic alternatives. The in-vitro activities of seven fluoroquinolone and macrolide compounds were tested against 23 clinical isolates of M. tuberculosis, including 17 multidrug-resistant strains. Sparfloxacin was the most active fluoroquinolone, with MICs of < or = 1 mg/L for all tested strains, followed by levofloxacin and ciprofloxacin. Trovafloxacin had no inhibitory activity at the concentrations tested. The MICs of the macrolides were generally higher, clarithromycin being the most active with MICs of < or = 8 mg/L for eight of the 23 strains.