Patients with acute nonlymphocytic leukemia frequently die of infection before cytotoxic therapy has had an opportunity to be effective. Prevention of infection might lead to increased remissions and, consequently, prolonged survival time. To establish the types and causes of infection, for 2½ years 48 patients have had extensive microbiologic surveillance cultures taken repetitively, beginning at admission. Each organism was defined as either part of the base-line flora or hospital acquired. All patients acquired multiple potential pathogens during hospitalization. These cultural data, in conjunction with observation of all infectious episodes, indicate that most infections arise from the patient's own flora. In 47% of these microbiologically documented infections, however, the pathogens had become part of the patient's resident flora after being acquired from the hospital environment. Measures to prevent infections in these patients must include reducing the acquisition of potential pathogens, especially Pseudomonas aeruginosa.