Combinations of fluoroquinolones with other antimicrobial agents have been extensively investigated. Combinations of fluoroquinolones with aminoglycosides, beta-lactams, imidazoles, macrolides and clindamycin infrequently show synergy against Enterobacteriaceae and gram-positive bacteria. These combinations rarely show antagonism. Combinations of rifampin with fluoroquinolones tested against Staphylococcus aureus have been reported to show synergy and antagonism, and in vitro results have not correlated with results of animal infection experiments. Against Pseudomonas aeruginosa combinations of antipseudomonas penicillins or imipenem with fluoroquinolones are synergistic for 20% to 50% of isolates in vitro and also are synergistic in animal models of infection, whereas combinations of aminoglycosides with fluoroquinolones rarely show synergy against Pseudomonas aeruginosa. Against anaerobic species such as Bacteroides fragilis combinations of fluoroquinolones with clindamycin, anti-anaerobic penicillins, cephalosporins or imidazoles are occasionally synergistic but usually indifferent. Ciprofloxacin and ofloxacin combined with antituberculosis agents have activity against Mycobacterium tuberculosis and atypical mycobacteria. In general, fluoroquinolones should be combined with other agents not to achieve synergy, which is extremely variable, but to provide activity against bacteria inadequately inhibited by the fluoroquinolones.