Combinations of aztreonam/vancomycin, aztreonam/vancomycin/amikacin, and moxalactam/ticarcillin were compared in a prospective randomized trial as empiric therapy for febrile neutropenic cancer patients. Vancomycin was added to aztreonam to provide coverage against gram-positive organisms. Of 535 febrile episodes included in the study, 455 were evaluable. The aztreonam/vancomycin and aztreonam/vancomycin/amikacin combinations were both more effective than the moxalactam/ticarcillin combination in a total of 244 episodes of documented infection. The difference was due to the fact that both aztreonam-containing combinations were more effective than the moxalactam/ticarcillin combination in documented gram-positive infections. The three regimens were equally effective in 67 documented infections due to a single gram-negative bacterial species. (The response rates were 87, 86 and 94 percent for the aztreonam/vancomycin, aztreonam/vancomycin/amikacin, and moxalactam/ticarcillin combinations, respectively.) Aztreonam was effective as the single active antibiotic in the treatment of gram-negative infections in neutropenic patients; however, it must be used in combination with another antibiotic to provide gram-positive coverage.