The aim of the present study was to explore the antibacterial activity of the levofloxacin (LVX) and ceftazidime (CAZ) combination compared with the amikacin (AMK)/CAZ combination against Pseudomonas aeruginosa. Minimum inhibitory concentrations (MICs) were determined according to NCCLS. FIC indices (Fl) were calculated by the checkerboard technique. CAZ combined with LVX or AMK yielded Fls indicating synergism (Fl < or = 0.5) for 71/102 (69.6%) and 81/102 (79.4%) (p = 0.108), indifference (FI > 0.5-4) for 24/102 (23.5%) and 12/102 (11.7%) (p = 0.027), and antagonism (Fl > 4) for 7/102 (6.8%) and 9/102 (8.8%) (p = 0.602) strains, respectively. In vivo, CAZ/LVX was as bactericidal as CAZ/AMK combination. Our results support the potential role of LVX as an alternative to AMK in the combination therapy with CAZ in the treatment of P. aeruginosa severe infections. Anyway, further investigations and clinical trials are awaited until any definitive conclusions can be drawn.