Combinations of piperacillin (PIP) with 3 systemic fluoroquinolones: pefloxacin (PEF), ofloxacin (OFL) and ciprofloxacin (CIP) were evaluated by checkerboard technique (bacteriostatic activity) and by time-killing curve technique (bactericidal activity as a function of time) for 4 bacterial strains with following MICs (micrograms/ml): 1 E. coli (PIP: 1, PEF: 0.12, OFL: 0.06, CIP: 0.016); 1 S. marcescens (0.25, 0.06, 0.06, 0.016); 2 P. aeruginosa (2, 1, 0.5, 0.12 and 4, 2, 2, 0.25). Bacteriostatic activity of the 3 combinations showed only different or additive effects (index FIC: 0.62 to 1.5). If the bactericidal activity was defined as a less than or equal to 3 log 10 decrease in CFU/ml in 3-6 h and less than or equal to 4 log 10 in 6-24 h, PIP was not bactericidal at MIC x 8 for all strains; nevertheless, combinations of PIP 2 + PEF 0.25, OFL 0.12 or CIP 0.016 on E. coli and PIP 1 + PEF 0.25, OFL 0.25 or CIP 0.06 on S. marcescens showed bactericidal activity, superior to each antibiotic singly. For P. aeruginosa a less than or equal to 4 log 10 decrease in 6-24 h was observed only in combination with PIP 16 + PEF 1, OFL 1 or CIP 0.25 and PIP 32 + PEF 4, OFL 4 or CIP 0.5. Combinations of PIP with quinolones showed synergistic effects: bactericidal activity was more rapid and prolonged with such combinations at concentrations near MICs and obtained with usual therapeutic doses.