Two antibiotic regimens were assessed, imipenem as monotherapy and ceftazidime plus vancomycin as combination therapy, for initial empiric therapy in febrile neutropenic children with cancer. In a prospective randomized trial of 89 evaluable consecutive episodes, 45 were treated with imipenem and 44 with ceftazidime-vancomycin. In 87% of the episodes the neutropenia was severe. Of the 89 episodes 20% were bacteremias, 10% were clinically defined focal infections and 70% were considered fevers of unknown origin. The initial treatment was successful in 82% of the imipenem group and 59% of the ceftazidime plus vancomycin group. Both regimens were well-tolerated. There was no mortality, probably owing to the prompt admission and institution of antimicrobial therapy. All of the patients were treated until neutrophil recovery; no recurrent infections were seen. In conclusion imipenem monotherapy was well-tolerated and effective as initial therapy for fever in neutropenia in children.