One hundred febrile episodes in 89 neutropenic patients after cytotoxic chemotherapy were randomized to be treated with either ceftazidime or imipenem as initial monotherapy. The clinical characteristics of the two groups of patients were comparable. The response of the fever in patients who received imipenem was significantly better than that in those who received ceftazidime (77 versus 56%, respectively; P = 0.04), especially in those with microbiologically documented infection (81 versus 33%, respectively; P = 0.02). The in vitro susceptibilities and the clinical responses suggested that, with the possible exception of Pseudomonas spp., imipenem was more effective than ceftazidime in treating neutropenic infections caused by both gram-positive and -negative organisms. An additional 23 and 21% of the patients in the ceftazidime and imipenem groups, respectively, responded to the addition of cloxacillin and amikacin following failure of monotherapy. The majority of the treatment failures, relapses, and superinfections were related to resistant infective organisms such as methicillin-resistant Staphylococcus spp. and Pseudomonas spp. or disseminated fungal infections.