Aztreonam plus vancomycin (AV), aztreonam plus vancomycin and amikacin (AVA), and moxalactam plus ticarcillin (MT) were compared in an ongoing, randomized, prospective trial of the treatment of febrile episodes in neutropenic patients with cancer. Vancomycin was combined with aztreonam to provide coverage against gram-positive bacteria. Patients with gram-negative bacterial infections who were given AV in effect received single-agent therapy with aztreonam. Overall, AVA was more effective than MT and somewhat more effective than AV in the treatment of 170 documented infections. AV and AVA were each more effective than MT in the treatment of 29 gram-positive infections (response rates of 90%, 80%, and 43%, respectively). The three regimens were equally effective in the treatment of 39 aerobic gram-negative infections (response rates of 88%, 100%, and 100% for AV, AVA, and MT, respectively). Thus far, the addition of amikacin to the AV regimen appears to offer no advantage in the treatment of documented gram-negative infections.