Synergistic activity between both azlocillin and mezlocillin and aminoglycosides or cefazolin could be demonstrated by checkerboard dilution, isobologram, and killing curve techniques. Azlocillin and mezlocillin combined with gentamicin, netilmicin, or amikacin were synergistic against Escherichia coli, Klebsiella, Citrobacter, Enterobacter, Serratia, and indole-positive Proteus. Synergy was observed with isolates that were susceptible or resistant to azlocillin or mezlocillin. Synergy was seen most often when azlocillin or mezlocillin were combined with amikacin, gentamicin, or netilmicin against Pseudomonas aeruginosa. The combination of mezlocillin and an aminoglycoside produced synergy more often than did carbenicillin plus an aminoglycoside. No antagonism was seen when aminoglycoside antibiotics were combined with azlocillin or mezlocillin. Cefazolin was synergistic against Pseudomonas, Providencia, P. mirabilis, indole-positive Proteus, Citrobacter, Klebsiella, and Escherichia coli, when combined with azlocillin or mezlocillin. However, the combination of either agent with cefazolin was antagonistic when tested against selected indole-positive Proteus and Enterobacter isolates.