Minimum inhibitory concentrations of carbenicillin, ticarcillin, and BL-P1654 were determined for 89 clinical isolates of Pseudomonas aeruginosa. Ticarcillin was generally twice as active and BL-P1654 eight to 16 times as active as carbenicillin. Usually carbenicillin and ticarcillin killed at the same concentration or twice the concentration needed to inhibit, whereas 400 mug of BL-P1654 per ml was not bactericidal for the majority of isolates tested. The inhibitory effect of all three drugs varied markedly with the size of bacterial inoculum. When therapeutically achievable concentrations were used, adding gentamicin enhanced the inhibitory and bactericidal activity of all three penicillin derivatives for the majority of isolates. However, inhibition of isolates highly resistant to gentamicin was not improved by combining the semisynthetic penicillins with gentamicin.