To evaluate the mortality and morbidity associated with early discontinuation of intravenously administered antibiotics, we prospectively examined the incidence and cause of recurrent fever in patients with persistent neutropenia who responded to a short course of intravenous antibiotic therapy. Preventive measures included the use of oral ciprofloxacin as prophylaxis for infection by gram-negative bacteria during the entire neutropenic episode. The rate of response to either initial or modified intravenous antibiotic therapy was 96% (149 of 156 episodes of fever). Eighty-five patients had an episode of persistent neutropenia (median duration, 7 days; range, 1-36 days) after they responded to treatment. Seven of these patients had recurrent fever, including 2 with bacteriologically documented infections, 4 with probable fungal pneumonia, and 1 with documented pneumonia due to Aspergillus fumigatus. Two patients with probable fungal pneumonia died, while the other infectious episodes resolved completely. These results do not support the continuation of intravenous antibiotic therapy for febrile patients with persistent neutropenia who have responded to the antibiotic regimen while receiving prophylaxis with oral ciprofloxacin.