Fifty-three clinical isolates of Klebsiella and fifty-one clinical isolates of Pseudomonas aeruginosa, twenty-six of which were carbenicillin-(CARB) resistant, were tested for susceptibility to mezlocillin (MEZ), azlocillin (AZL), and piperacillin (PIP), both alone and in combination with tobramycin (TOB) using the microtiter broth diluent method and an inoculum density of 10(6) CFU/ml. The Klebsiella were highly resistant to TOB, MEZ, and PIP (MIC90: 8, greater than 256, greater than 128 micrograms/ml, respectively). Synergy was demonstrated in 53 percent (PIP/TOB) and 51 percent (MEZ/TOB). An indifferent response was observed in 47 percent (PIP/TOB) and 49 percent MEZ/TOB of the Klebsiella. PIP, MEZ, and AZL in combination with TOB showed synergism against CARB-resistant Pseudomonas in less than 10 percent of the strains tested. Synergy could be demonstrated against CARB-susceptible Pseudomonas with the combinations PIP/TOB, AZL/TOB, and MEZ/TOB in 12 percent, 12 percent, and 24 percent, respectively, of the twenty-five strains tested. Indifferent effects were observed in 84 percent, 88 percent, and 76 percent, respectively, of these same CARB-susceptible strains. These data suggest that there is no significant difference in the incidence of synergy with these new penicillins and tobramycin against either Pseudomonas or Klebsiella.