In an open, prospective pilot study of pediatric cancer patients, 23 episodes of fever and neutropenia were treated with intravenous and then oral antibiotics. After 72 hours, patients were changed from intravenous to oral antibiotics if the following criteria were met: negative blood cultures, temperature 38.0 degrees C or lower for 24 hours, absolute neutrophil count less than 0.5 x 10(9)/L, and absence of clinical sepsis. Three patients (13%) had recurrent fever. Intravenous antibiotics were reinstituted in two of these three patients, and oral antibiotics were continued in the third. Fever was believed to be related to relapsed leukemia in one of the three patients. No focus of infection was defined in the other two, and both had good clinical outcomes. The study suggests that this approach to therapy is feasible and can be safely used for selected patients who are anticipated to have a short duration of neutropenia.