An abbreviated three-dimensional checkerboard titration method was devised to determine whether synergistic interaction of three antimicrobial agents could be found against multidrug-resistant bacteria. Pseudomonas maltophilia was used as the test organism because of its resistance to most commercially available antimicrobial agents, including those active against Pseudomonas aeruginosa. Three-dimensional isobolograms with concave surfaces were formed when synergy occurred. Triple combinations of gentamicin-carbenicillin-rifampin (mean fractional inhibitory concentration index, 0.32) and trimethoprim/sulfamethoxazole-carbenicillin-rifampin (mean fractional inhibitory concentration index, 0.18) were consistently synergistic against 14 clinical isolates of P. maltophilia.