One hundred and thirty-nine febrile episodes in 120 patients were treated with sisomicin after a combination of carbenicillin and a cephalosporin antibiotic had failed. These patients were randomized to receive sisomicin either by continuous or by intermittent infusion. The response rate for patients treated with sisomicin was 61 percent by continuous infusion and 46 percent by intermittent infusion, which was not statistically significant. Pneumonia, septicemia, and soft tissue infections were the most frequent infections. Most (96 percent) of the identified pathogens were gram-negative bacilli with the most frequent being Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. The response rate was higher in those patients whose neutrophil count increased or remained the same while on therapy. The worst response was obtained if there was a decrease in the neutrophil count during therapy. The major toxicity of sisomicin was found to be azotemia and occurred in 17 percent of episodes treated by continuous infusion and in 21 percent treated by intermittent infusion. Hearing loss in the high frequency range occurred in five patients. Sisomicin is effective in the treatment of gram negative infections in neutropenic cancer patients.