Patients with hematologic malignancies were randomly assigned to receive cefuroxime (group A) or tobramycin plus ampicillin (Group B) during 86 febrile episodes. In both regimens carbenicillin was added during neutropenia (71% of all episodes: groups C and D). The most common type of infection was pneumonia (48% alone; 72% with other sites involved), which accounted for a high fatality rate (15%); the highest rate occurred during septicemia with pneumonia (50%). The overall response rate to initial therapy was 63% without significant differences among the four regimens. The worst prognosis was observed in neutropenic patients without granulocyte recovery. When initial and cross-over trials were combined, there were favorable outcomes in 90% of all cases. Cefuroxime alone seems to be as effective as tobramycin plus ampicillin in the treatment of infections in hematologic malignancies. No side effects could be attributed to the cefuroxime-containing regimens.