Serial surveys on the etiology of nosocomial bacteremia have been conducted over a period of years at Boston City Hospital (Boston) and Grady Memorial Hospital (Atlanta). A comparison of the information from these surveys with that from single-period surveys at 10 other hospitals in the United States illustrates changes in the etiology of nosocomial bloodstream infection over the past five decades. Prominent trends include an increased frequency of episodes of polymicrobial bacteremia, an increased frequency of sequential episodes of bacteremia in the same patient, a resurgence of infection due to Staphylococcus aureus, the recognition of Staphylococcus epidermidis and other components of the endogenous flora as pathogens, and an increased prominence of enterococci, gram-negative aerobic bacilli, anaerobes, and fungi as agents of nosocomial bloodstream infection. Changes in the etiology of nosocomial infection that are not illustrated by the data on bacteremia include an increased appreciation of the importance of viruses, a diminished role for Mycobacterium tuberculosis, and the description of new and unusual pathogens, usually in patients with compromised host defenses. This last trend can be expected to continue.