Owing to increasing resistance in Pseudomonas aeruginosa, empirical drug regimens may include agents to which some strains may be resistant. The purpose of this study was to evaluate the in vitro activities of different combinations of cephalosporin plus fluoroquinolone against P. aeruginosa isolates with varying susceptibility to the study drugs. Broth microdilution susceptibility testing was performed with 10 clinical isolates of P. aeruginosa. The bactericidal activity of cefepime or ceftazidime alone and in combination with ciprofloxacin, levofloxacin, gatifloxacin or moxifloxacin was evaluated using time–kill methods. Colony counts were determined at 0, 4, 8 and 24 h, using antimicrobial concentrations of 0.5 × MIC. All procedures were performed in duplicate. Synergy was defined as a >2-log decrease in cfu/mL at 24 h compared with the single most active agent. The MICs for tested strains were: ceftazidime 0.75–32, cefepime 0.125–8, ciprofloxacin 0.0078–8, levofloxacin 0.023–16, gatifloxacin 0.023–16 and moxifloxacin 0.0521–32 mg/L. Four strains were susceptible to all drugs, two strains were cephalosporin susceptible and fluoroquinolone resistant, and two strains were cephalosporin resistant and fluoroquinolone susceptible. Two strains were resistant or intermediately susceptible to all drugs. Various cephalosporin and fluoroquinolone combinations were synergic against P. aeruginosa, including strains resistant to one or both agents in combination. No synergy was observed in two strains susceptible to all drugs. There were no differences noted between different cephalosporin and fluoroquinolone combinations. Concentrations used in this study are clinically achievable with recommended regimens in most cases.